Pharm Flashcards
GABA role and system
inhibitory
role: regulator, sedation, sleep, pain, anxiety
system: inhibitory interneuron
glutamate role and system
excitatory
role: excitatory and regulates Ca2+ influx; neuroplasticity, learning, pain, sensory regulation and perception
system: NMDA AMPA receptors throughout brain
Ach role and system
role: movement
system: pontomesencephalo-tegmental, medial septal nucleus, basal nucleus of Meynert
norepi role and system
role: alertness, attention, stress, fear, anxiety, SNS
system: locus ceruleus
dopamine role and system
role: movement; reward, pleasure, motivation, focus, conditioning
system: nigrostriatal, mesocorticolimbic
serotonin role and system
role: depression, anxiety, sleep, appetite, pain, aggression, impulse
system: raphe nuclei
streptokinase
- Derived from bacteria so less expensive
- MOA: enhance conversion of plasminogen to plasmin to enhance fibrin degradation & subsequent clot
- AE: severe allergic reaction
alteplase
- MOA: analogue of human tPA to enhance conversion of plasminogen to plasmin to enhance fibrin degradation & subsequent clot
- AE: severe bleeding (reverse w aminocaproic), wait 24 hrs to start ASA
reverse severe bleeding via tPAs with __________
aminocaproic acid
tenecteplase, reteplase
- Mutated longer acting forms tPA
- MOA: enhance conversion of plasminogen to plasmin to enhance fibrin degradation & subsequent clot
- AE: severe bleeding (reverse w aminocaproic), wait 24 hrs to start ASA
aspirin (ASA)
- MOA: Irreversible COX Inhibitor that inactivates platelet COX-1 enzyme
- Long-duration decrease thromboxane (TXA2)
- Ideal preventative if patient can tolerate
- AE: bleeding, hemorrhage, allergic reaction (asthmatic), GI
dipyridamole
- MOA: Phosphodiesterase inhibitor prolongs cAMP (plt agg inhibitor)
- Administered in prep w/ aspirin (ERDP/ASA)
- Increases serum adenosine (antiplatelet actions)
- Increases prostacyclin levels (counteracts TXA2 effects)
clopidogrel
- MOA: Activated in liver to ADP receptor antagonist to inhibit clot formation (see cascade above)
- Alternative if can’t take aspirin
warfarin
- MOA: competitively inhibits vitamin K epoxide reductase (VKOR) to decrease vit K regeneration (co-factor necessary for clotting)
- AE: major CYP inhibitor – drug interactions, bleeding (reverse with vit K)
- Slow onset – 5 days (not for emergencies)
- Indications: hx of thromboembolisms, afib, stroke prevention
dabigatran
- MOA: competitive antagonist of thrombin=direct thrombin inhibitor
- Short-acting, rapid onset (benefits in early stroke treatment), orally available, Doesn’t block other clotting factors, Less drug interactions than warfarin
- AE: bleeding but has a short half-life so self-limiting
- Indications: active thrombosis, prevention of stroke in afib
SSRI (fluoxdetine, escitalopram) MOA
selectively blocks the 5HT reuptake transporters (SERT) to increase 5HT
SSRI adverse and blackbox
o Adverse
- Nausea, GI, sexual dysfunction, drug interactions (CYP2D6), weight changes, anxiety
o Black box
- Serotonin syndrome – OD can cause hyper -tension, -thermia, -reflexia, -stimuation (HR)
• Tx: cyproheptadine – 5HT receptor antagonist to block serotonin
- Suicidal ideation in pediatrics
SNRI (venlafaxine, desvenlafaxine) MOA
Blocks SERT and NE reuptake transporters (NET) to increase 5HT and NE
buproprion MOA
blocks dopamine reuptake transporters (DAT) and NET to increase DA and NE
for depression, SAD, quit smoking
TCA MOA (-triptylines)
blocks NET and SERT with higher affinity for NET to increase 5HT and NE
TCA adverse and OD
o Adverse
- Hypotension, constipation, urinary retention, blurry vision, dry mouth, tachycardia, weight gain, sedative, v-fib arrhythmia (due to fast Na+ channel myocyte block)
o Overdose
- Can be toxic, 3Cs – cardiac, convulsion and coma
• Tx: bicarbonate to direct drug away from heart via pH, saline for HoTN
trazodone MOA
antagonist at SERT and 5HT2A to change 5HT auto-receptors over time
mirtazapine MOA
a2 auto-receptor and 5HT2A receptor antagonist, also histamine antagonist
trazodone adverse
priapism, weight gain, sedative
MAOi MOA (Phenelzine, selegiline)
inhibits MAO inhibits metabolism of NE and serotonin
3rd line antidepressant
MAOi adverse
- MAO inhibits metabolism of tyramine, which can build up and increase catecholamines
• Avoid tyramine rich foods (wine, cheese), can have dangerous CV and HTN effects - High toxicity, HTN, serotonin syndrome, agitation, anxiety, stroke, seizures
- Avoid with sympathomimetics!
lithium MOA
uncompetitive inhibitor of inositol monophosphatase, an enzyme that regenerates inositol, so Li depletes free inositol (within 5 days) and stabilizes mood by slowing neurotransmitter receptors (5HT) coupled to PLC 2nd messenger system
lithium adverse
Weight gain, polydipsia and polyuria, hypothyroidism, tremor
Teratogen (Ebstein’s anomaly), renal dysfunction, cardiac arrhythmias, nephrogenic DI, neurotoxicity
valproate MOA
potent anticonvulsant and mood stabilizer, exact MOA of mood stabilization unknown
VG Na+ C blocker, also blocks VG T-Type CC channels
• Maybe blocks VGNaC, enhances GABA, inhibits GSK3 and decreases PKC
valproate adverse
Hair loss, weight gain, hepatotoxic, pancreatitis
1st trimester teratogen= spina bifida, low IQ; also excreted in breast milk
lamotrigine adverse
SJS-TENS, dizzy, diplopia
lamotrigine MOA
anticonvulsant VGNaC, weak voltage-gated calcium channel (VGCC) inhibitor, reduces glutamate release
carbamazepine/oxcarbazepine MOA
potent VGNaC blocker anticonvulsants
benzodiazepines (diazepam, lorazepam, clonazepam) MOA
anxiolytic, sedative, muscle relaxant, anticonvulsant and amnestic effects via GABA, potent centrally acting
baclofen MOA
GABAb agonist that increases potassium conductance promotes hyperpolarization
- Enhances presynaptic inhibition and decreases release of excitatory NTs
gabapentin MOA
inhibits voltage-gated calcium channels (VGCC), reduces excessive glutamatergic activity, CNS depressant/ analgesic properties for pain
carisoprodol MOA
metabolized to meprobamate (barbiturate) to activate GABAa which leads to CNS depression
riluzole MOA
- Block Na channels and decrease Ca influx, reduces glutamatergic activity
- Used for neuroprotective properties in ALS
tizanidine MOA
a2 adrenergic agonist that reduces muscle spasms and pain
for ALS, MS and stroke
cyclobenzaprine MOA
antimuscarinic
TCA like
orphenadrine MOA
antimuscarinic and antihistamine
metaxalone MOA
CNS depressant that relaxes via central pathway but NT changes unknown
botox MOA
blocks Ach release to produce flaccid paralysis and reduces spasms
tizanidine adverse
dry mouth, drowsy, hypotension
L-Dopa MOA
• Gets converted to DA by dopa-decarboxylase in brain (3%) peripherally (97%)
• Anti-Parkinson effect is related to central D2 agonism on post-synaptic neurons
- If used alone, L-dopa mostly effect peripheral neurons which is not ideal
for parkinsons
Carbidopa
inhibits dopa-decarboxylase without crossing BBB
• ↓peripheral conversion; lets more L-Dopa go to brain
bromocriptine MOA
ergot related non-selective but potent D2 receptor agonist
for parkinsons
apomorphine MOA
non-ergot non-selective DA agonist
for parkinsons
pramipexole MOA
D3 agonist
for parkinsons
ropinirole MOA
D2 agonist
for parkinsons
Selegiline and rasagiline MOA
MAO-B inhibitor that prolongs brain DA
Tolcapone, Entacapone MOA
COMT inhibitor that increase L-Dopa into brain
Amantadine MOA
antiviral that increase DA and is adenosine antagonist
Amantadine adverse
seizure, psychosis, restlessness, liver dysfx, edema, livdeo reticulari
Tolcapone, Entacapone adverse
dyskinesia, insomnia, nausea, orthostatic HoTN, vomiting, confusion, dizziness; tolcapone has block box for liver toxicity
benzotropine, trihexyphenidyl MOA
- Antagonist at muscarinic receptors to ↓unopposed Ach excitation from ↓DA
- Good adjunct with L-Dopa to control drooling and tremor
benzotropine, trihexyphenidyl adverse
- Dry mouth, constipation, blurred vision, urinary retention
- Can’t poop, can’t pee, can’t sweat, can’t see – cholinergic
Tetrabenzazine (and Deutetrabenzazine – slower onset
Reversible VMAT2 inhibitor that depletes DA and reduces hyperkinesia for Huntington’s
donepezil MOA
reduce breakdown of central acetylcholine (Ach) = more Ach available to stimulate muscarinic receptors to improve memory & cognition in AD
long half life, 2D6 and 3A4
galantamine MOA
reduce breakdown of central acetylcholine (Ach) = more Ach available to stimulate muscarinic receptors to improve memory & cognition in AD
2D6 and 3A4
rivastigmine MOA
reduce breakdown of central acetylcholine (Ach) = more Ach available to stimulate muscarinic receptors to improve memory & cognition in AD
short half life
Ach esterase inhibitor adverse
GI (diarrhea, drooling), bradycardia, sweating, pulmonary, confusion if OD
memantine MOA
antagonizes NMDA receptor to block glutamate excitotoxicity
Local anesthesia effects sensory or motor fibers more
sensory
Local anesthesia effects delta or motor fibers more
delta
Local anesthesia effects myelinated or unmyelinated fibers more
myelinated
during inflammation, pH is more _____, so must inject _____ with anesthesia
acidic
NaHCO3
Esters - anesthetic
long
short
surface
tetracine
procaine
benzocaine and cocaine
Amides- anesthetic
long
medium
short
bupivacaine, ropivacaine, etidocaine
lidocaine
articaine
mepvacaine - vasoconstricts
Naloxone
Mu antagonist for opioid overdose
morphine
Mu, Kappa and Delta agonist
hydrophilic
• Decrease immune function, constipation, miosis, itching, flushing, delirium
• Concern for asthmatics (histamine) and renal dysfunction
hydromorphone and oxymorphone
more potent than morphine with shorter duration and less histamine
fentanyl
full opioid agonist for severe pian
remifentanil metabolism
by plasma esterase in blood not in liver
methadone
Mu agonist and NMDA antagonist
sub for heroin addicts
oxycodone and hydrocodone
less Mu agonist, but good oral availability
codeine
partial Mu agonist with tussive effects
metabolized by 2D6
tramadol
partial Mu agonist with NET and SERT blocking
buprenorphine
Mu and Kappa agonist
less severe withdrawal
can’t reverse OD with naloxone
meperidine
opioid agonist that also blocks SERT
can cause seizures
nalbuphine
kappa agonist
mu antagonist
less addictive potential
pentazocine
kappa and mu agonist with less nausea but hallucinations
butorphanol
kappa and mu agonist that comes in nasal spray
triptan MOA
• 5HT agonist on intracranial blood vessels and sensory nerves to constrict cerebral vessels and decrease pain
1st line MH abortive
ergotamine, dihydroergotamine MOA
alpha1 adrenergic partial agonist with non-selective 5HT agonism on vessels
ergotamine, dihydroergotamine black box
gangrene and fatal ischemia if used with 3A4 inhibitor
lasmiditan
new neuronally active antimigraine agents (NAAMA)
5HT1F agonist that targets brainstem and trigeminal neurons to reduce release of CGRP and major peptide mediator without vasoconstriction
valproate and topiramate for MH
block VGNaC and augment GABA
benzodiazepams MOA
bind to ionotropic GABAa receptors and facilitate Cl influx when endogenous GABA activates GABAa to hyperpolarize membrane – allosteric!
benzodiazepams with no active metabolites
lorazepam
oxazepam
benzodiazepam overdose
flumazenil
buspirone MOA
5HT1a auto-receptor partial agonist that has a non-BZD mechanism to alter serotonin firing, no rebound or withdrawal symptoms
SSRI approved for OCD
Fluvoxamine
Glatiramer MOA and for what
for MS
• Spares myelin basic protein by acting as a decoy to the immune system
• Induces and activates regulatory suppressor CD8+ T-cells specific for myelin antigen and increases anti-inflammatory IL-10
natalizumab MOA and for what
for MS
• Monoclonal antibody to a4 integrin chain on VLA4 – prevents VLA4 from binding VCAM1 so myelin-reactive T-cells can’t cross the BBB
ocrelizumab MOA and for what
for MS
anti-CD20 monoclonal antibody that targets mature B-cells attacking the myelin sheaths of healthy neurons
fingolimod MOA and for what
forMS
binds to sphingosine PO4 receptors and reduces CNS lymphocyte penetration
terflunomide
for MS
active metabolite of leflunomide
inhibits pyridimine synthesis –> immunosuppression
dimethyl fumartae
for MS
activates NRF2 to immunomodulate
drugs of abuse increase _______ ______
mesocorticolimbic dopamine
drugs of abuse MOAs EtOH barbiturate GHB marijuana
EtOH - GABAa Cl influx and B-endorphin release
barbiturate - allosteric GABAa activator
GHB - GABAb agonist –> K+ influx
marijuana - binds cannabinoids
methamphetamine MOA
taken up by DAT, binds to VMAT and reduces vesicular packing of DA
promotes reverse transport
methamphetamine abuse signs
pruritis, bruxism, anorexia, aggression, anxiety, psychosis, seizures, paranoia
methylene dioxymethamphetamine (MDMA) ((Ecstasy)) MOA
taken up by SERT, NET & DAT and binds to VMAT and acts as reverse transporter
pharm tx for EtOH abuse
disulfiram
naltrexone
acamprosate
pharm tx for opioid abuse
methadone
buprenorphine/naloxone
first generation antipsychotics
D2 antagonists
haloperidol, chlorpromazine
treats positive symptoms
has EPS adverse
atypical antipsychotics
5-HT2A antagonism, weaker D2 antagonists
aripiprazole, risperidone
less EPS adverse, more metabolic syndromes
clozapine
good for treatment resistant schizophrenia after 2 failures
minimal EPS risk
high agranulocytosis risk
valbenazine MOA
inhibits VMAT2 to release DA
to reduce tardive dyskinesia
black boxes for antipsychotics
long QT
increase mortality in elderly
caffeine MOA
- Competitive adenosine receptor antagonist that decreases blood flow to brain
- Also, a PDE inhibitor that blocks cAMP degradation, so increase cAMP
nicotine MOA
- Increases influx of Na+ and is excitatory by acting at cholinergic receptors
- Activates mesocorticolimbic dopamine
methylphenidate (Ritalin) MOA
blocks DAT & NET transporters; increases synaptic dopamine and norepinephrine
amphetamine (Adderall) MOA
increase monoamine release via reverse transport at DAT & NET transporter
reverse transporter
atomoxetine MOA
- Selective Inhibition of NET increases synaptic NE similar to TCA antidepressants
- Increased NE in reticular system should increase attention
acute relief of status epilepticus
lorazepam/diazepam
if no response -> IV fosphenytoin -> IV phenobarbital -> valproate or anesthesia
phenobarbital
GABA mimetic used as 2nd line anticonvulsant
phenytoin MOA
for epilepsy
bind to inactivated state of voltage gated Na channels and prevent reopening and prolong inactivation of neurons
phenytoin kinetics
- 1st order kinetics at low dose
* Zero order kinetics at saturation
phenytoin adverse
- Gingival hyperplasia, hepatotoxic, arrythmias, CV toxicity, HoTN
- Teratogen – Fetal Hydantoin Syndrome
carbamazepine adverse
for epilepsy
• Aplastic anemia, agranulocytosis, skin disorders
• Sign of toxicity – vestibular, diplopia, hematologic
levetiracetum MOA
for epilepsy
binds presynaptic synaptic vesicular protein SV2A to increase GABA and reduce glutamate
ethosuximide MOA
for epilepsy
“petit mal drug” that inhibits voltage gated T-Type Ca 2+ channel
gabapentin and pregabalin
for epilepsy
bind to a2delta subunit of Ca channel
tiagabine MOA
inhibits GAT1 neuronal GAB reuptake site to increase synaptic GABA
cephalosporins that cross the blood brain barrier (5)
ceftazidime, ceftriaxone, cefotaxime, cefuroxime, cefepime
treatment for cocaine OD
BZDs
succinylcholine
depolarizing neuromuscular blocker that binds and blocks open gate; tetanic contraction followed by flaccid paralysis
what can tubocurarine / atracurium / rocuronium cause?
malignant hyperthermia
dantrolene
treat malignant hyperthermia by blocking RyR1 Ca influx
IV anesthetic examples (6)
thiopental methohexital propofol etomidate dexmedetomidine ketamine
inhaled anesthetic examples (4)
halothane, isolurane, desflurane, methoxyfluarane
relationship of BGPC to induction of anesthesia
inverse
such that lower BGPC has faster induction
relationship of MAAC to potency of anesthesia
inverse
such that lower MAAC has greater potency
