Def of epilepsy
Group of disorders characterized by excessive excitability of neurons in the CNS
Can produce a variety of symptoms ranging from brief periods of unconsciousness to violent convulsions
May also cause problems with learning, memory, and mood
Initiated by sy
Partial seizures
simple partial: discrete, no loss of function, last 20-60 seconds
Complex partial: impaired consciousness, lasts 45-90 seconds
Secondarily generalized: start as simple or complex and then progress to tonic-clonic
Generalized seizures
tonic-clonic: manifests as major convulsions with tonic-clonic phases, markedly impaired conciousness and follows with CNS depression, neuronal discharge to both hemispheres of brain
Absence: loss of consciousness for brief period of time, may have 100's
Lennox-Gastaut Syndrome
severe form of epilepsy that develops during preschool years
characterized by developmental delay and mixture of partial and generalized seizures
Can be very difficult to treat
Goal of treatment for AED
reduce seizures to a level that allows the patient to live as normal a life as possible
Balance the desire for complete seizure control with the acceptability of side effects
Non drug therapies for epilepsy
Neurosurgery: used to cure patients with temporal lobe epilepsy, very effective but remains under utilized
Vagus nerve stimulation: medical device for reducing seizures, used in conjunction with drug therapy and usually results in a simpler treatment regi
AED drug selection
requires physical, neurologic, and lab evaluations along with thorough health history
Patients usually try many drugs before regimen is successful and well tolerated
AED's: therapeutic considerations
monitoring plasma levels: is target zone being hit? especially helpful when monitoring major convulsive disorders, less important for absence seizures
Promoting patient adherence: seizure control is greatly dependent on this, don't stop taking meds
Withdr
Phenytoin: uses, mechanism of action, absorption
Therapeutic uses: can be used to treat all forms of epilepsy except absence seizures, esp effective against tonic-clonic seizures, partial seizures, used in older children and adults; can also be used to treat cardiac dysrhythmias
Mechanism of action: sel
Phenytoin: adverse effects
Nystagums is relatively common, sedation, ataxia, diplopia, cognitive impairment, gingival hyperplasia (supplementation with folic acid, good dental hygiene, and gum massage can decrease this effect), measles like rash which can progress to Steven-Johnson
Pheytoin: drug interactions
decreases effects of oral contraceptives, warfarin, and glucocorticoids because it stimulated the synthesis of hepatic drug-metabolizing enzymes--people need to up the dosages of these drugs to achieve desired effect
diazepam, isoniazid, cimetidine, valpr
Carbamazepine: MOA, therapeutic uses
MOA: same as phenytoin, delayed recovery of sodium channels from their inactivated state
Therapeutic uses: epilepsy (TC, simple partial and complex partial, preferred agent because less side effects), bipolar disorder (often used for people who are refrac
Carbamazepine: adverse effects
minimal effects on cognitive function
neurological effects: visual disturbances like nystagmus, blurred vision, diplopia, ataxia, vertigo, unsteadiness, and headache (tolerance usually develops)
hematologic effects: leukopenia, anemia, thrombocytopenia, f
Carbamazepine: drug interactions
accelerated inactivation of oral contraceptives and warfarin because it induces hepatic drug-metabolizing enzymes
Phenytoin and Phenobarbital: induces hepatic metabolism, decreases effects of all drugs
Avoid grapefruit juice
Valproic Acid: therapeutic uses
seizures: first line agents for all partial and generalized seizures
Bipolar disorder
Migraine headache prophylaxis
Valproic Acid: adverse effects
minimal sedation and cognitive impairment
GI effects are the most common (take with food, enteric coated if possible), hepatoxicity and pancreatistis are rare but serious, teratogenic, hyperammonemia
Valproic acid: drug interactions
phenobarbital, phenytoin, topiramate, carbapenem antibiotics
Phenobarbital
Uses: epilepsy, partial and generalized tonic-clonic seizures)
Promotes sleep and sedation because it is a benzodiazapine
Ethosuximide
only indication is for absence seizures
generally devoid of significant adverse effects and interactions, initially may cause drowsiness, dizziness, and lethargy, N&V which can be avoided if taken with food
Rare but serious side effects: SLE, leukopenia,
Gabapentin
Therapeutic uses: adjunctive therapy of partial seizures, off label uses: neuropathic pain, prophylaxis of migraine, treatment for biromyalgia, relief of post-menopausal hot flashes
Management of generalized convulsive SE
SE: series of TC seizures lasting 20-30 minutes
Goals of treatment: maintain ventilation, correct hypoglycemia, initially treat seizures with lorazepam (generally preferred) or diazepam, then initiate or continue long-term suppression therapy (phenytoin o
Causes of muscle spasm and spasticity, treatment
causes: epilepsy, hypocalcemia, trauma (localized skeletal muscle injury), acute and chronic pain syndromes
Treatment: physical measures include immobilization of affected muscle, cold compresses, whirlpool baths, physical therapy, drug therapy for spasms
centrally acting muscle relaxants: MOA, therapeutic uses
MOA: diazepam which enhances effects of GABA and tizanidine which acts as an agonist at presynaptic alpha2 receptors
Therapeutic uses: used to relieve localized spasm resulting from muscle injury
Centrally acting muscle relaxants: adverse effects
produce generalized depression of the CNS resulting in drowsiness, dizziness, and lightheadedness, avoid alcohol and other CNS depressants
Hepatic toxicity: trizanidine can cause liver damage, LFTs should be run
Physical dependence: therapty should be wit
Drugs for spasticity
baclofen, diazepam, and dantrolene
most common uses are for MS and CP, but can be used for traumatic spinal cord lesions and stroke
baclofen and diazepam work on CNS, dantrolene acts directly on skeletal muscle
Baclofen: MOA and therapeutic uses
MOA: acts within the spinal cord to suppress hyperactive reflexes involved in regulation of muscle movement, may act by mimicking GABA because they are structural analouges
Therapeutic uses: MS, spinal cord injury, CP but NOT STROKE; suppress resistance t
Baclofen: adverse effects
CNS: drowsiness, dizziness, weakness, fatigue, overdose can cause coma and respiratory depression, no antidote
Withdrawal has been associated with adverse reactions, intrathecal stoppage can be very dangerous
GI disturbances: N&V, urinary retention
Diazepam
only benzodiazepine labeled for treating spasticity
works on CNS to suppress spasticity by mimicking actions of GABA, does no affect skeletal muscles directly
Adverse effect: sedation
Dantrolene: MOA and therapeutic uses
MOA: acts directly on skeletal muscle by suppressing the release of calcium from the sarcoplasmic reticulum
Uses: relieves spasticity caused by MS, CP, spinal cord injury, malignant hyperthermia
Dantrolene: adverse effects
hepatic toxicity
Muscle weakness/reduction in strength (weigh benefits against harm), drowsiness, diarrhea, anorexia, N&V, acne-like rash
Clinical presentation of schizo
disordered thinking and reduced ability to comprehend reality
three types of symptoms: positive, negative, cognitive
characterized by acute episodes (delusions and hallucinations are frequently prominent), residual symptoms (suspiciousness, poor anxiety m
FGA's: MOA and uses
MOA: block variety of receptors within and outside CNS including dopamine (D2 receptors in brain), ACh, histamine, NE
Therapeutic uses: schizophrenia, bipolar disorder, Tourette's syndrome, prevention of emesis, delusional disorders, schizoaffective disor
FGA's adverse effects
drugs are overall very safe
Extrapyramidal symptoms (EPS) including acute dystonia, parkinsonism, akathisia (uncontrollable need to be in motion), tardive dyskinesia (no cure, prevention is key)
neuroleptic malignant syndrome (rare by serious, risk of dea
FGA's drug interactions, toxicity
anticholinergic drugs: avoid these, including antihistimines, OTC sleep aids
CNS depressents: intensifies CNS depression
Levodopa and direct dopamine receptor agonists: may counteract the antipsychotic effects of neuroleptics
Toxicity: extremely rare, ove
Haloperidol
high-potency agent, causes more early EPF but less sedation, orthostatic hypotension, and anticholingeric effects
Used to treat schizophrenia and acute psychosis, preferred agent for Tourette's syndrome
Adverse reactions: early EPS including acute dystoni
Loxapine
medium potency agent indicated only for schizophrenia
Chlorpromazine
Low potency agent used for schizophrenia and other psychotic disorder like schizoaffective disorder and manic phase of bipolar disorder
Kinetics: PO, IM, IV
Adverse effects: sedation, orthostatic hypotension, and anticholinergic effects, neuroendocrine ef
Clozapine: MOA, therapeutic uses
MOA: blockade of receptors for dopamine and serotonin, NE, histamine, ACh
Therapeutic uses: schizophrenia, levodopa induced psychosis
Clozapine: adverse effects and interactions
sedation and weight gain, diabetes, dyslipidemia, anti-cholinergic effects, AGRANULOCYTOSIS, seizures, EPS (very minimally), myocarditis, orthostatic hypotension, mortality in elderly patients with dementia related psychosis
Interactions: anything that su
Risperidone
approved for schizophrenia, acute bipolar, aggressive tendencies in autism spectrum
rapid absorption not affected by food
adverse effects generally infrequent and mild
Olazapine
MOA: block receptors for serotonin, dopamine, histoamin, ACh, NE
Used in schizophrenia and bipolar
High risk for metabolic effects
Quetiapine
blocks receptors for serotonin, dopaimine, histamine, ACh, NE
Used to treat schizophrenia, major depression, acute mania in bipolar disorder
adverse effects: metabolic, cataracts
drug interactions: CYP3A4, drugs that induce these enzymes cause drug to hav
Ziprasidone
Same as all others
used to treat schizo and bipolar mania
adverse effect: QT wave prolongation
Aripiprazole
dopamine system stabilizer", does not block cholinergic receptors
approved for schizophrenia, acute bipolar mania, major depressive disorder, agitation associated with schizo or bipolar mania, irritability associated with autism spectrum disorder
kinetic
Depot preparations
long acting, injectable formulations used for long term maintenance therapy of schizophrenia
no evidence that depot preparations pose an increased risk of side effects
three preparations are available: haloperidol decanoate, fluphenazine decanoat, risperi
Adjunctive therapy for schizophrenia
benzodiazepines, antidepressants
Antidepressent groups
tricyclic antidepressants
SSRI's
SNRI's
MAOI's
Atypical antidepressents
General info about depression
most common psychiatric disorder
30% of the US population will experience some form of depression during their lifetime
Approx 5% of adult population is depressent
Incidence in women is twice that of men
Risk of suicide is high in depression
Often goes un
Clinical features of depression
depressed mood, loss of pleasure or interest, insomnia or hypersomnia, anorexia, etc
Depression: pathogenesis
complex and incomplete
Possible factors include genetic heritage, difficult childhood, chronic low self-esteem
Monoamine hypothesis: depression is caused by functional insufficiency of monoamine NT's
depression: treatment modalities
pharmacotherapy is primary therapy
depression-specific psychotherapy (eg-cognitive behavioral therapy)
ECT: when drugs and psychotherapy have not worked, when a rapid response is needed, for severely depressed and suicidal patients, elderaly patients at r
Suicide risk with antidepressents
may increase suicidal tendency early in treatment
Patients should be observed closely for suicidality, worsening mood, changes in behavior
precautions: prescriptions should be written for the smallest number of doses consistent with good patient managemen
SSRI's: general info
Introduced in 1987, most commonly prescribed type of antidepressent, as effective as TCA's but do not cause hypotension, sedation, or anticholinergic effects, overdose does not cause cardiac toxicity, death by overdose is extremely rare
Fluoxetine
AKA Prozac
MOA: produces selective inhibition of serotonin reuptake, works only on serotonin so it does not cause hypotension, sedation, etc; produces CNS excitation
Therapeutic uses: primarily used to treat major depression but can also be used for OCD,
Sertaline
AKA Zoloft
MOA: blocks uptake of serotonin and dopamine, causes CNS stimulation, minimal effects on seizure threshold
Therapeutic uses: major depression, panic disorder, OCD, PTSD, PMDD, social anxiety disorder
Adverse effects: headache, nausea, tremor, d
Fluovoxamine
aka fluvox
MOA: inhibition of serotonin reuptake
Uses: OCD
Half life: 15 hours
Side effects: N&V, constipation, weight gain, dry mouth, headache, sexual dysfunction, abnormal liver function, sedative effects
Interactions: MAOI's
Paroxetine
AKA Paxil
MOA: inhibition of serotonin uptake
Uses: major depression, OCD, social phobia, panic disorder, generalized anxiety disorder, PTSD, DMDD
Citalopram
AKA Celexa
MOA: inhibition of serotonin reuptake
Therapeutic uses: major depression
side effects: nausea, somnolence, dry mouth, sexual dysfunction, can cause neonatal abstinence syndrome
Interactions: MAOI's
Escitalopram
Lexapro
S-isomer of citalopram, better tolerated
Side effects: nausea, insomnia, somnolence, sweating, fatigue
SSRI's
fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram, escitalpram
SNRI's
Venlafaxine, duloxetine, desvenlafaxine
block neuronal reuptake of serotonin and NE with minimal effects on other transmitters and receptors
venlafaxine
Effexor
MOA: blocks NE and serotonin uptake
Therapeutic uses: major depression, generalized anxiety disorder, social anxiety disorder
side effects: nausea, headache, anorexia, nervousness, sweating, somnolence, insomnia, weight loss, diastolic hypertensio
desvenlafaxine
Pristiq
MOA: strong inhibitor of serotonin and NE reuptake
therapeutic use: only major depression
Side effects: nausea, headache, dizziness, insomnia, diarrhea, dry mouth, sweating, constipation, ED, decreased libido
duloxetine
cymbalta
MOA: inhibits serotonin and NE reuptake, weakly inhibits dopamine reuptake
Therapeutic uses: depression, pain associated with diabetic peripheral neuropathy
Adverse effects: nausea, somnolence, dry mouth, sweating, insomnia, blurred vision, liver
Tricyclic antidepressents: MOA, therapeutic uses
Drugs of first choice for many patients with major depression
MOA: blocks neuronal uptake of NE and serotonin
Therapeutic uses: depression, bipolar, neuropathic pain, chronic insomnia, ADD, ADHD, panic disorder, OCD
Tricyclic antidepressants: adverse effects, toxicity, drug interactions
Adverse effects: orthostatic hypotension, anticholinergic effects, diaphoresis, sedation, cardiac toxicity, seizures, hypomania, yawngasm
Drug interactions: MAOI's, direct acting sympathomimetic drugs increased in response to TCA's, indirect acting sympat
MAOI's: general info
second or third choice antidepressant for most patients
As effective as SSRI's and TCA's but more dangerous
Risk of triggering hypertensive crisis if patient eats foods rich in tyramine
Drug of choice for atypical depression
MAOI's: mechanism of action
convert monoamine NT's like NE, serotonin, and dopamine into inactive products
Inactive tyramine and other biogenic amines
Two forms of MAOs in body: MAO-A and MAO-B
All MOA's in use cause irreversible inhibition
MAOI: therapeutic uses, adverse effects, drug interactions
Uses: depression, bulimia nervosa, OCD, panic disorders
Adverse effects: CNS stimulation, orthostatic hypotension, hypertensive crisis from dietary tyramine
Drug interactions: indirect-acting sympathomimetic agents, interaction secondary to inhibition of
Selegiline
Transdermal MAOI
used to treat depression, much lower risk of hypertensive crisis with transdermal route vs. oral route
eneters system without going through GI tract
Adverse effects still occur when used with sympathomimetic drugs
Bupropioin: actions and uses
Atypical antidepressent
acts as a stimulant and suppresses appetite, antidepressent effects begin in 1-3 weeks
Does not affect serotonergic, cholinergic, or histaminergic transmission
does not cause weight gain, increases sexual desire and pleasure
Bupropion: adverse effects and drug interactions
adverse effects: can cause seizures, agitation, tremor, tachycardia, tremor, blurred vision, dizziness, headache, insomnia, dry mouth, GI upset, constipation, weight loss
Interactions: MAOI's can increase the risk of bupropion toxicity
nonconventional drugs for depression
ketamine: anesthetic agent usually used in children but can be useful in severely/acutely depressed adults
St. John's wort: mild to moderate depression, but interacts with other antidepressants so it is important to get through drug history
Electroconvulsive therapy
outside the realm of pharmacology
valuable in treatment for depression
two desirable characteristics: effectiveness and rapid onset
Two primary types of patients: those who have failed to respond to other drugs, severely depressed, suicidal patients
can t
Transcranial magnetic therapy
outside realm of pharmacology
reserved for major depression
Employs an insulated magnetic coil, placed against the scalp, to deliver pulsed magnetic fields to the left dorsolateral prefrontal cortex
daily 40 minute sessions for 6 weeks
adverse effects inc
Vagus nerve stimulation
for long term therapy of treatment-resistant depression when at least four antidepressent drugs have failed
MOA: implanted device that delivers electrical pulses to vagus nerve
side effects: hoarseness, voice alteration, cough, dyspnea
Light therapy
exposure to bright light, effective treatment for SAD or nonseasonal major depression
may enhance serotonergic neurotransmission
the more intense the light, the greater the response
Bipolar disorder: general info
cyclic disorder characterized by recurrent fluctuations in mood, episodes of mania and depression persist for months without treatment
Treatment includes drugs and psychotherapy
subdivided into two categories:
bipolar disorder I: manic or mixed episodes u
Drug therapy for BD
Mood stabilizers: lithium, relieves symptoms during manic and depressive episodes, prevents recurrence of manic and depressive episodes, does not worsen symptoms of mania or depression, does not accelerate the rate of cycling
Antipsychotics: given during
BD: promoting compliance
short-term hospitalization, long-term prophylactic therapy, education for both patient and family
BD: non-drug therapy
education for patient and family
psychotherapy (individual, group, family)
ECT as last resort
Mood stabilizers for BP
lithium, valporate, and carbamazine are all first line agents
antiepileptic drugs: valproate, carbamazepine (reduces symptoms, protects against recurrence of mania and depression, target trough plasma level: 4-12mcg/mL), Lamotrigine (indicated for long te
Lithium: chemistry, MOA, therapeutic uses
Chemistry: simple inorganic ion found naturally in animal tissues
MOA: altered distribution of certain ions, altered synthesis and release of NE, serotonin, and dopamine, mediated intracellular responses to neurotransmitters, shown to facilitate regenerat
Lithium: pharmacokinetics, adverse effects
pharm: short half life, excreted by kidneys, lithium excretion reduced when sodium levels are low, plasma levels should be less than 1.5 mEq/L
Adverse effects with excessive lithium levels: occur when levels greater than 1.5, monitor levels every 2-3 days
Lithium: drug interactions and preparations
interactions: diuretics, NSAIDs, Anticholinergic drugs
Preparations: lithium carbonate, citrate; dosages are highly individualized
Antipsychotic drugs in BPD
used to acutely control symptoms during manic episodes
long term to help stablize mood
benefit patients with or without psychotic symptoms
five antipsychotics approved for use: olanzapine, quetiapine, riperidone, aripirazole, ziprasidone
Zolpidem
Ambien
benzo-like drug
used for short term management of insomnia
Zaleplon
Sonata
Benzo-like drug, new class of hypnotic called pyrazolopyrimidines
Used in short term treatment of insomnia
prolonged use does not appear to cause tolerance
Eszopiclone
Lunesta
Benzo-like drug
used for treating insomnia, no limitation on how long it can be used
Ramelteon
Melatonin agonist
relatively new hypnotic
works by activating melatonin receptors
approved for chronic insomnia, difficulty with sleep onset
rapid onset, about 30 minutes
Sedative-hypnotic drugs
drugs that depress CNS function, primarily used to treat anxiety and and insomnia
distinction between antianxiety and hypnotic effects is often a matter of dosage
Benzo's: general info
drug of choice for anxiety and insomnia, used to induce general anesthesia
safer than general CNS depressants with lower potential for abuse
produce less tolerance and physical dependence, fewer drug interactions
Most prescribed is lorazepam and alprazola
Benzo's: MOA, therapeutic uses
MOA: potentiates GABA the inhibitory NT
Therapeutic uses: anxiety, insomnia, seizure disorders, muscle spasm, alcohol withdrawal, panic disorder, perioperative applications
Benzo's: adverse effects, interactions, tolerance, toxicity
adverse effects: CNS depression, anterograde amnesia, sleep driving, paradoxical effects, respiratory depression, abuse, not for use in pregs or lactation, allergic reactions
Interactions: CNS depressants
Tolerance: overtime development of tolerance to so
Barbituates: classes, MOA, effects
Classifications: ultrashort-acting, short to intermediate acting, long acting (phenobarbital)
MOA: binds to the GABA receptor-chloride channel complex
Pharm effects: CNS depression, modest depression in HR and BP, induction of hepatic drug-metabolizing en
Barbituates: tolerance, pharm, uses
tolerance: develops to many but not all CNS effects, very little tolerance develops to respiratory depression; prolonged use leads to physical dependence
pharm: more highly lipid soluable have quicker onset and shorter duration and the opposite is also tr
Barbituates: interactions, adverse effects, toxicity
interactions: CNS depressants like alcohol, interactions resulting from induction of drug-metabolizing enzymes (contraceptives, warfarin), chloral hydrate, meprobamate
Adverse effects: respiratory depression, suicide, abuse, not good for use during pregs
Miscellaneous sedative-hypnotics
basic pharm profile: nonselective CNS depressants, actions like those of barbituates, acute overdose resembles poisoning with barbituates, avoid during pregs and lactation
includes chloral hydrate, meprobamate, paralehyde
Drugs used to treat insomnia
benzos, benzo like drugs, ramelton, trazodone, doxepin, antihistamines, alternative medicines
Anxiety
an uncomfortable state with psychological and physical components
characterized by fear, apprehension, dread, and uneasiness, among the most common of psychiatric illnesses
Types of disorders include GAD, panic disorder, OCD, social anxiety disorder, PTSD
generalized anxiety disorder
characteristics: uncontrollable worrying lasting six months or longer, not situational anxiety
Non-drug treatment: supportive therapy, CBT, biofeedback, relaxation training
Drug treatment: Benzo's, BuSpar, antidepressents (paroxetine, escitalopram, venlaf
Busprinone
non-CNS depressent, does not cause sedation, no abuse potential, does not intensify the effects of CNS depressents, anxiolytic effects develop slowly, well absorbed following oral administration
adverse effects: dizziness, nausea, headache, nervousness, l
Panic disorder
characterized by palpitations, pounding heart, racing heart, fear of losing control, etc
treatment: CBT, antidepressents (SSRI, TCA, MAOI), benzodiazepines (first line drugs for panic disorder)
OCD
characteristics: potentially disabling condition, persistent obsessions and compulsions
Treatment: behavioral therapy, drug therapy (SSRI's like citalopram, excitalopram, fluoxetine, fluvoxamine, paroxetine, sertaline OR clomipramine which is less well to
Social anxiety disorder
characteristics: intense, irrational fear that one might be scrutinized by others, generalized and nongeneralized, very debilitating, one of the most common psychiatric disorders
treatment: psychotherapy, drug therapy (benzo's, SSRI's, propranolol for per
PTSD
characteristics: develops following a traumatic events, involves re-experiencing the event, avoiding reminders of the event, persistent state of hyperarousal
Treatment: psychotherapy with drugs, psychotherapy alone
Immunizations: general
purpose is to protect against infectious diseases, most effective method is to create a highly immune population, universal vaccination is the goal
Vaccines carry risk, but risk of disease are much greater
Immunizations: definitions
vaccine: causes immune system to manufacture antibodies directed against specific microbe
Killed vs live vaccines
toxoid: bacterial toxin changed to non-toxic form, protects against toxin but does not kill bacteria, diphtheria and tetanus are examples
imm
Why report vaccine-preventable disease?
determines whether outbreak is occurring
evaluates prevention and control strategies
evaluates the impact of national immunization policies and practices
Immunization records
national childhood vaccine act of 1986 requires a permanent record of each mandated vaccination including date, route and site, vaccine type, manufacturer, lot number, expiration date, name, addy, title of person administering
Reason to record: ensure app
Who is at risk for receiving vaccines?
immunocompromised children are at special risk from live vaccines, health conditions include: congenital immunodeficiency, HIV infection, leukemia, lymphoma, generalized malignancy, therapy with radiation, cytotoxic cancer drugs, high-dose gluccocorticoid
Target diseases for immunizations
measles, mumps, rubella, diphtheria, tetanus, pertussis, polio, H. influenza type B, varicella, hep B and A, pneumococcal infection, meningococcal infection, influenza, rotovirus, genital human papillomavirus infection
specific vaccines and toxoids
measles, mumps, and rubella virus vaccine (MMR, contraindicated in pregs)
DTaP
poliovirus
H. influenza type by (one of the safest vaccines)
varicella (don't administer to pregs, allergy to neomycin, history of gelatin allergy, immunocomp)
Hep B (assess fo
Immunosuppresents
inhibit immune response
used to prevent organ rejection and for treatment of autoimmune diseases
Toxcity: increased risk for infection and neoplasms
calcineurin inhibitors
principle use is for prevention of organ rejection in transplant recipients
cyclosporine and tacrolimus are the most effective IS available
differ in structure but share same mechanism: inhibition of calcineurin which suppresses production of IL-2 which i
Cyclosporine
MOA: suppresses the production of IL-2, interferon gamma, and other cytokines
Uses: drug of choice for organ rejection of allogenic transplants of kidney, liver, and heart, some autoimmune diseases, usually given with prednisone
adverse effects: nephrotox
Tacrolimus
alternative to cyclosporine, somewhat effective but also more toxic, used concurrently with glucocorticoids
Uses: prophylaxis of organ rejection (kidney, liver, heart)
Same MOA as cylosporine: suppresses the production of IL-2, interferon gamma, and other
mTOR inhibitors
enzyme known as mammalian target of rapamycin which is a protein kinase that helps regulate cell growth, proliferation, and survival
structurally similar to tacrolimus but somewhat different in mechanism in that is does not inhibit calcineurin; ultimately
Sirolimus
actions: only indication is for prevention of renal transplant rejection, used in conjunction with glucocorticoids
Adverse effects: increased risk of infection, raises levels of cholesterol and triglycerides, risk of renal injury, sever complications of l
Everolimus
Used for prevention of kidney transplant rejection
MOA: prevents activation of T and B cells
adverse effects: peripheral edema, constipation, HTN, nausea, anemia, UTI, hyperlipidemia, toxic to developing fetus
drug and food interactions: drugs that inhibi
glucocorticoids
Used widely to suppress immune response, suppression of allograft rejection, treatment of asthma, RA, SLE, and MS
Large doses used to prevent rejection
Can increase risk of infection, thinning of skin, bone dissolution with fracture, impaired growth inchi
cytotoxic drugs
suppress immune response by killing B and T lymphocytes undergoing proliferation
non-specific so they are toxic to all proliferating cells
adverse effects include bone marrow suppression which can lead to neutropenia and thrombocytopenia, also GI disturba
azathioprine
MOA: suppresses cell-mediated and humoral immune responses by inhibiting DNA synthesis
Therapeutic uses: adjuvant treatment with transplants, autoimmune disorders
adverse effects: neutropenia, thrombocytopenia, mutagenic and teratogenic, neoplasms
cyclophosphamide
cytotoxic drug used for anticancer
methotrexate
cytotoxic
used for cancer, autoimmune disorders
Mitoxantrone
cytotoxic
anticancer drug
reduction of neurologic disability and clinical relapse for MS patient
dangerous drug reserved for patient with are not response to safer drugs
mycophenolate
approved for prophylaxis of organ rejection, acts on B and T cells to inhibit inosine monophosphate dehydrogenase
Antibodies as immunosuppressents
Muromonab-CD 3, basiliximab, lymphocyte immune globulin, antithymocyte
Muromonab CD3
monoclonal antibody
uses: blocks all t-cell function, prevents acute rejection of transplants, depletes T cells before bone marrow transplant
Adverse effects: fever, chills, dyspnea, chest pain, N&V
Basiliximab
monoclonal antibodies, blocks activation of T cells by IL-2, prophylaxisis of acute organ rejection
Histamine
endogenous compound found in specialized cells and play an important role in allergic reactions and regulation of gastric acid secretion
distribution: found in practically all body tissues and especially in skin, lungs, and GI tract, low content in plasma
H1 receptors
cause vasodilation in skin of the face and upper body, can cause hypotension
increased capillary permeability resulting in edema
bronchoconstriction but NOT the cause of asthma attacks
CNS effect: histamine plays a role in cognition, memory, and sleep-wak
H2 receptors
involved in secretion of gastric acid
histamine can act directly on parietal cells to promote gastric acid release
Allergic response
mediated by histamine and other compounds including protaglandins, leukotrienes, tryptase
Mild allergic response
caused largely by histamine acting at H1 receptors resulting in itching, localized edema
hay fever, mild transfusion reactions, acute uticaria
usually responsive to antihistamine therapy
Severe allergic response
anaphylaxis ---> anaphylactic shock
bronchonstriction, hypotension, edema of the glotis, histamine plays a major role, leukotrienes are the principal mediators, antihistamines are of little use in treatment, epinephrine is the drug of choice
H1 antagonists
First generation are highly sedating as compared to second generation
MOA: block actions of histamine at H1 receptors, some bind to muscarinic receptors
Peripheral effects: reduce localized flushing, reduce itching and pain
Effects on CNS: overdose can re
H1 Antagonists: adverse effects
sedation, dizziness, fatigue, coordination problems, confusion, GI effects (N&V, loss of appetite, constipation--give with food), anticholinergic effects (drying of mucus membranes, urinary hesitancy, constipation, palpitations so avoid giving to people w
Antihistamines: high risk patients
contraindicated in third trimester of pregs, nursing mothers, and newborn infants
use in caution in young children, older adults, and patients who's conditions may be aggravated by muscarinic blockade
H1 antagonists: second generation
fexofenadine
cetirizine
levocetirizine
loratadine
desloratide
Allergic rhinitis
inflammatory disorder of the upper airway, lower airway, and eyes
symptoms include sneezing, rhinorrhea, pruritis, nasal congestion, for some people can also cause conjunctivitis, sinusitis, and asthma
Seasonal and perennial, triggered by airborne allerge
Drug classes for allergic rhinitis
oral antihistamines
intranasal glucocorticoids
sympathomimetics
Oral antihistamines
for allergic rhinitis
does not reduce nasal congestion
most effective if taken prophylactically
adverse effects are milk, include sedation with first generation, anticholinergic effects
Azelastine nasal spray: only intranasal antihistimaine available, ben
Intranasal glucocorticoids
first choice, most effective for treatment and prevention of rhinitis
mild adverse effects include drying of nasal mucosa or sore throat
rarely, systemic effects include adrenal suppression and slowing of linear pediatric growth
intranasal cromolyyn
extremely safe, but only moderately effective, suppresses release of histamines from mast cells, best used for prophylaxis not for treatment, effects take 1-2 weeks to develop
Sympathomimetics
reduce nasal congestion (do not reduce rhinorrhea, sneezing, or itching), activate alpha1-adrenergic receptors on nasal blood vessels
adverse effects: rebound congestion (especially with topical), CNS stimulation (restlessness, irritability, anxiety, inso
Drugs for cough
antitussives
opioid: codine
non opioid: dextromethophan, diphenyldramine
Common cold
acute upper respiratory viral infection with rhinorrhea, nasal congestion, cough, sneeze, sore throat, headache, hoarseness, malaise, myalgia
fever common in kids, but not in adults
self-limiting and usually benign
no cure, just treat symptoms
combination
Pediatric OTC cold remedies
use with caution in young children
no proof of efficacy or safety but proof of harm, avoid OTC cold remedies in children younger than 2 years of age, use only products labelled for peds use, consult a healthcare professional before giving to a child, read
Asthma: general info
chronic inflammatory disorder of the airway
characterisitic signs and symptoms: sense of breathlessness, tightening of chest, wheezing, dyspnea, cough
Cause: immune mediated airway inflammation
Patho: symptoms of asthma result from a combination of inflam
Inhalation drug treatment for asthma
Advantages: therapeutic effects are enhanced, systemic effects are minimized, relief of acute attacks is rapid
Three types: metered-dose inhalers (hand-held device, hand-eye coordination is required, only 10% of drug reaches lungs), dry-powder inhaler (de
Anti-inflammatory drugs
Foundation of asthma therapy, taken daily for long term control, principle anti-inflammatory drugs are glucocorticoids
Asthma glucocorticoids
include budesonide and fluticasone
considered to be the most effective anti-asthma drugs available, reduce bronchial hyperreactivity
also decrease airway mucus production and increase the number of bronchial beta2 receptors as well as their responsiveness
Leukotriene modifiders
suppress effects of leukotrienes, less effective than glucocorticoids, available agents include zileuton, zafirlukast, montelukast
Cromolyn
used for prophylaxis, not quick relief, suppresses inflammation, not a bronchodilator
route: nebulizer, MDI
adverse effects: safest of all antiasthma medication, cough, bronchospasm
Bronchodilators
provide symptomatic relief but do not alter the underlying disease process
in almost all cases, patients taking a bronchodilator should also be taking a glucocorticoid for long-term suppression of inflammation
principle bronchodilators are beta2-adrenergi
Methylxanthines
benefits derive primarily from bronchodilation, Theophyline: have a narrow therapeutic index, plasma levels 10-20 mcg/mL, toxicity can result (not often prescribed because of this)
other examples include aminophyline and dyphyline
Glucocorticoid/LABA combinations
available combinations include fluticasone/salmeterol and budesonide/formoterol
indicated for long-term maintenance in adults and children, not recommended for initial therapy
Management of chronic asthma
test of lung function: forced expiratory volume in 1 second (most useful test of lung function, results compared to predicted normal value for healthy person of similar age, sex, height, and weight), forced vital capacity is the total volume of air a pati
drugs for acute severe exacerbations of asthma
requires immediate attention
goal is to relieve airway obstruction and hypoxemia, and normalized lung function as quickly as possible
initial therapy consists of giving oxygen to relieve hypoxemia, giving system glucocorticoids to reduce airway inflammati