Exam 6 (drugs only) Flashcards
Tx for acute MS relapse
High dose IV methylprednisolone = 1 mg
2 disease modifying drugs used to tx MS
- MoA
- side effects
- reduction in relapse rate
- administration routes
- Beta-interferon
- MoA - inhibits pro-inflammatory cytokines, T-cell proliferation, CNS trafficking
- Side effects - myalgia and chills
- Administered - subq and IM
- broad impact on inflammation - Glatiramer acetate
- mixture of amino acids
- similar efficacy and side effects as above
- give SQ
BOTH - 30 to 40% reduction in relapse rate
BOTH - tx relapsing remitting and 2ndary progressive MS
What 2 drugs are more effective than beta-interferon and glatiramer acetate for txing relapsing remitting and 2ndary progressive MS?
- MoA
- side effects
- administration route
NATALIZUMAB
- MoA
- binds to integrin-cellular adhesion molecule
- blocks lymphocytes-endothelial binding which prevents cell from crossing BBB - Administered through IV monthly
- Side effects -> PML in 0.2%
FINGOLIMOD
- MoA
- blocks egress of lymphocytes from lymph nodes and spleen - Administered orally (unique)
- Side effects
- risk of heart block in some w/ initial dose ONLY
- 1 case of PML reported
2 other oral agents to tx MS
dimethyl fumarate and teriflunomide
List 2 anticholinergic medications discussed in the dementia lecture
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
List 2 medications with anticholinergic action
Amitriptyline (Elavil)
Diphenyhydramine (Benadryl)
Tx for absence epilepsy
- include dosing
- standard and atypical
- Ethosuximide 20 mg/kg/day: Standard
* Valproic Acid 20 mg/kg/day: If atypical
Major DA systems in the CNS
- highest concentration of DA found in which pathway?
- which one is the therapeutic target of antipsychotics?
- side effects
- Nigrostriatal
- SN to corpus striatum
- majority of DA here
- SIDE EFFECT -> EPS (movement disorders) - Mesolimbic
- VTA to nucleus accumbens
- THERAPEUTIC SITE - Mesocortical
- VTA to frontal cortex
- THERAPEUTIC SITE - Hypothalamus
- arcuate nucleus to medial eminence
- tuberoinfundibular
- prolactin release regulation
- SIDE EFFECT -> ENDOCRINE DISORDERS
Which drug inhibits reuptake in NE neurons but not DA neurons?
Desipramine
MoA of typical antipsychotics
D2 receptor antagonists
Extrapyramidal DA side effects of typical antipsychotics
- Acute dystonia - Spasm of muscles of face, tongue, neck, and back
- Akathisia - Motor restlessness
- Parkinsonism - Rigidity, tremor, shuffling gait
- Tardive dyskinesia - Oral-facial involuntary movements, choreiform movement of extremities
- late sign
Neuroleptic Malignant Syndrome
- cause
- symptoms
- treatment
Reaction to antipsychotics (haldol hyperthermia)
Symptoms
- Hyperthermia
- Autonomic Instability
- Muscle Rigidity
FEVER (from board)
- fever
- encephalopathy
- vitals unstable
- elevated enzymes
- rigidity of muscles
Treatment
1. Withdraw typical antipsychotic
2. Cooling, hydration, supportive care
3. Dantrolene(muscle relaxant) for cooling
Bromocriptine (DA receptor agonist)
Endocrine DA side effects of typical antipsychotics
-hormonal change and effect
- Prolactin INCREASED
Increased lactation, gynecomastia, etc.
Inhibits ovulation, menses
Decreased adrenal corticosteroid secretion - Gonadotropins DECREASED
Inhibits ovulation, menses - Corticotropins DECREASED
Decreased adrenal corticosteroid secretion
Adverse (non-DA) peripheral effects phenothiazines (e.g., chlorpromazine)
3 groups
- Anticholinergic activity
- dry mouth
- blurred vision
- constipation - alpha-adrenoceptor blockade
- orthostatic hypoTN
- inhibition of ejaculation - Endocrine
- appetite increase
- weight gain
Huntington’s chorea can be txed with?
haloperidol - DA receptor antagonist
What is a major advantage in using atypical antipsychotics over typicals. Why do we get this advantage?
Much less EPS side effects (D2)
-not completely devoid but have a much higher therapeutic index than typicals
List 5 atypical antipsychotics (the ones in bold in the ppt)
Aripiprazole Olanzapine Clozapine Quetiapine Risperidone
It’s Atypical for Old Closets to Quietly Risper from A to Z
What’s a disadvantage of atypical antipsychotics? Give examples of this disadvantage
At normal doses, metabolic side effects are significant for atypical drugs
- weight gain
- metabolic problems
- type 2 diabetes
Young and old must be given more attention
Serious side effect of Clozapine
- percent of patients affected
- etiology of the side effect?
Agranulocytosis (1-2% of patients; genetic). Testing Essential.
Which antipsychotic is a partial agonist at D2 DA receptors? Is it typical or atypical
Aripiprazole - atypical
Compare the efficacy between typical and atypical antipsychotics
Similar efficacy
~70% of patients
Acamprosate
- MoA
- use
Reduces the excitatory actions of glutamate at the NMDA receptor
-prevent severe w/drawal from alcohol
Disulfiram (antabuse)
- MoA
- side effect
• Inhibits aldehyde dehydrogenase (ALDH) • Use along with psychosocial support • Compliance is an issue • Patient needs to monitored o Specially if they have other issues (e.g. heart) • Not used as much anymore
Naltrexone
- MoA
- side effects
- check for what before starting?
- Good evidence
- Anti-relapse drug
- Most common side effects = nausea and headache
• Nonselective opiate antagonist
o Reduces the reward component of drinking
• Run a basic liver panel before starting
o Hep B and C
- Once a day pill
- Use in combination w/ psychosocial treatments for best effect
Acamprosate
- MoA
- used for
• Modulates the glutamate (indirectly blocks Glu effects on NMDA receptor)
• Diminishes post-acute withdrawal
o Weeks after people are off substances
o This time period is filled with discomfort for the patient
• Few side effects
Sustained release Naltrexone
- how is it administered?
- benefits?
- problems?
- Given IM
- New and expensive
- Addresses compliance
- Administered monthly
- Vivitrol
- Good for people with chaotic lives
Most effective plan to treat alcohol dependence? Least effective?
Naltrexone in combination with medical mngt. found most effective.
Behavioral intervention alone, least effective.
List 3 FDA approved pharmacological treatments for quitting nicotine
NRT
Bupropion SR
Varenicline tartate
NRTs
- types
- effect on quit rate
- precautions
- gum, spray, inhalation
- double the quit rate
- precautions include
1. pregnancy (class C)
2. CV diseases
Buproprion SR in Treating Nicotine Use Disorder
- precaution (2)
- contraindications (3)
- side effects (2)
- effect on quit rate
- dosing
-precaution in pregnancy and CV diseases
-contraindicated in patients with
seizures
eating disorders
MAOI use w/in the past 14 days
-side effects
insomnia
dry mouth
-double quit rate
-dosing
• Begin 1-2 weeks before quit date
• Start at 150mg qAM for 3 days then ↑ to 150mg BID
• Maintain this dosage for 7-12 weeks following quit dat
Varenicline tartate
- MoA
- used for
- unique benefit
- quit rate
MoA - partial agonist at the alpha4beta2 receptor
- causes inhibition of GABA’s inhibition of DA
- activates release of DA
Less cravings and w/drawal side effects
Smoking won’t lead to the same high
-leads to extinction
Triples quit rate short term
Long term quit rate less
List to off label meds for nicotine use disorder
Nortriptyline and clonidine
Nortriptyline
- precautions
- side effects
- quit rate
-precautions in pregnancy and those w/ CV disease
side effects
- sedation
- dry mouth
- urinary retention
- risk of OD and cardiotoxicity
-doubles the quit rate
Clonidine
- precautions
- risk of
- side effects
- quit rate
- preg and CV disease
- risk of rebound hypertension (taper dose)
- side effects -> dry mouth, drowsiness, sedation and constipation
- doubles quit rate
5 C’s of addiction
Chronic behavioral and mental disorder Control of use impaired Compulsive use Continued use despite harm Craving for the drug
Type 1 vs type 2 substance craving behavior
- trigger
- NTs involved
Type 1
- cue triggered
- NT: glutamate
Type 2
- stress triggered
- CRF in amygdala
- NE in brainstem
Major reward site for alcohol
endorphin release by stimulation of mu opiate receptor
How do stimulants (cocaine and amphetamines) work in the brain?
Enhance monoamine NT activity by inhibiting MAO reuptake in synapse
o DA – reward
o NE – physiological arousal
o 5-HT – elevated mood
Mechanism for alcohol w/drawal - 3 things
Decrease in number of GABA receptors
Upregulation of NMDA receptors
- leads to hyperexcitability
- lower seizure threshold
Autonomic hyperactivity
- inc noradrenergic activity in the LC
- Benzos blunt this by stimulating GABA
Opiate w/drawal mech and sxs
-how to reduce the sxs
o Internalization of mu opiate receptors
o Increased autonomic activity
o Hyperesthesia
-Increased perception of pain
o Dysphoria
o Admin opiate agonists mitigate sxs
o Clonidine diminishes noradrenergic effects for LC
- Alpha blocker
- Reduce the hyperactivity
o Nausea, vomiting, diarrhea
-Use antiemetic (e.g. Zofran)
Stimulant w/drawal
Deplete DA from reward center (KNOW THIS)
• Decreased or lack of substance
– Severe dysphoria and drug craving
– Sleep disturbances and fatigue
Topomax/topiramate for alcohol w/drawal
Anticonvulsants to regulate manic behavior
Opioid agonists for opiate detox
- methadone
- buprenorphine
- suboxone
Issue w/ using naltrexone for opiate detox
-must be opiate free for 7 days
BLOCK ANALGESIA
-lot of pain
Buprenorphine
- MoA
- why combined with naloxone (suboxone)
Partial mu agonist with HIGH AFFINITY
Precipitates w/dawal with recent opiate use
- displace opioid from receptor
- naloxone added to block action when used IV
Methadone MoA
- full mu agonist
- long acting
- low misuse potential
- tx the w/drawal sxs from opiates
Only activating antidepressant used to tx nicotine w/drawal
Bupropion
Best evidence for NRT use
High dose replacement w/ transdermal + oral breakthrough craving
chantix/varenicline
- MoA
- black box warning
- partial agonist at nicotinic receptor
- increased suicide risk
Arrange the therapies for depression based on most preferred to least
SSRI > SNRI > Atypicals > TCAs > MAOIs
Side effects of lithium
-decrease in what makes Li+ more toxic?
LMNOP Lithium side effects: -Movement (tremor) -Nephrogenic diabetes insipidus -HypOthyroidism -Pregnancy problems
Carbamazepine
- class
- MoA
- metabolism
- side effects/contraindications
- anticonvulsant
- enhances inhibitory action of GABA by inhibiting VG Na channels
- induced hepatic (CYP3A4) of itself
- lots of drug-drug ix at the level of hepatic metabolism
- serious skin rxns in HLA-58
- teratogenic (category D)
Valproic acid
- class
- MoA
- drug-drug ix?
- side effects/contraindications
- anticonvulsant
- inhibits Na and Ca channels -> activate GABA inhibitory effects
- drug-drug interactions due to high serum protein binding
- GI complaints; rare hepatic problems, tremor, sedation
- Teratogenic (Pregnancy Category D)
SSRIs - there are 4 (use mnemonic)
Flashbacks paralyze senior citizens
Fluoxetine, paroxetine, sertraline, citalopram
Side effects of tricyclic antidepressants
Tri-C’s: Cardiotoxicity, convulsion, coma
Major side effect of MAOI
hypertensive crisis especially when combined with 6mg tyramine
most common side effects seen with SSRIs?
sexual dysfx and GI probs
Name 2 SNRIs
Venlafaxine, duloxetine
general Rule for naming TCAs
all TCAs end in -iptyline or -ipramine except doxepin and amoxapine
imipramine
