Thrombolytics and MH Flashcards
stage 1 hemostasis - formation of platelet plug
activation of GP IIb/IIIa - fibrinogen bridges, platelet aggregation
stimulated by thromboxane A, thrombin, collagen, platelet activation factor, ADP
Stage 2 hemostasis - coagulation
thrombin –>conversion of fibrinogen to fibrin
intrinsic - contact activation pathway - blood exposure to collagen
OR
extrinsic-tissue factor pathway - trauma to vascular wall
pathways converge at Factor Xa
prevention of arterial thrombosis
Antiplatelet medication - prevents platelets from
clumping together to form a clot
damage often local
prevention of venous thrombosis
anticoagulants - disrupt coagulation cascade
damage is distant
anticoagulants contraindications/heparin
x-id - with risk for bleeding active hemorrhage, recent hemorrhagic stroke, active lumbar puncture, surgery on eye, brain, spinal cord, thrombocytopenia
Extreme cautions with Heparin
dissecting aneurysm, severe hypertension, hemophilia, recent (3mo) surgery, pregnancy, very recent abortion/miscarriage, recent GI bleed - PUD
Thrombolytics
“clot busters” - break up existing clot by speeding up conversion of plasminogen to plasmin
Anticoagulants
Prevent venous thrombosis
Heparin and derivatives
vitamin K antagonists - Warfarin
Direct Thrombin inhibitors
Factor Xa inhibitors
When are anticoagulants prophylactic? when are they therapeutic?
low dose=prophylactic dose
full dose=therapeutic dose/treatment dose
Heparin
admin’ed for procedures- open heart, ECMO, adjunct to thrombolytic in MI, renal dialysis/other invasive devices, *DVT - treatment and prevention, Rapid anticoagulation needs: PE or evolving stroke, low dose post-op to prevent venous thrombosis
preferred during pregnancy - does not cross placenta
ADR: bleeding/hemorrhage - internal, spinal/epidural hematoma
HIT, hypersensitivity
local- irritation, bruising, hematoma
IV or SQ - high risk medication - risk for bleeding, dosing variability - double checks
monitor labs - antifactor Xa, aPTT, platelet count
D-D interaction - antiplatelets and other anticoagulants
antidote - protamine sulfate
anticoagulant (heparin) use - risk of spinal/ hematoma
risk increased by:
-use of indwelling epidural catheter
-use of other anticoagulants (eg warfarin)
-use of antiplatelet drugs (eg aspirin, clopidogrel)
-hx of traumatic or repeated epidural or spinal
puncture
-hx of spinal deformity, spinal injury, spinal surgery
pts should be monitored for s/s of neurologic impairment
heparin antidote
protamine sulfate
Normal platelet values
150,000-400,000
INR
mechanical valve – 3-4,
Afib – 2-3
natural fibinolysis
destruction of clot via tissue plasminogen activator (tPA) - converts inactive plasminogen to active enzyme plasmin
plasmin degrades fibrin mesh and breaks up clot
natural fibinolysis
destruction of clot via tissue plasminogen activator (tPA) - converts inactive plasminogen to active enzyme plasmin
plasmin degrades fibrin mesh and breaks up clot
suspect HIT
-significant platelet loss - 30%
-thrombosis despite heparin therapy
if platelets <100,000
platelet counts should be monitored frequently during first 3 weeks of heparin use (2-3/wk)
Specific √ HIT Immunoassay
aPTT - activated partial thromboplastin time
normal value - 40 seconds
heparin at therapeutic levels - 60-80 seconds
used to titrate heparin dosage - if too long, reduce dose, if too short (<60sec)
measurements should be made frequently - every 4-6 hours during initial therapy, then once/day once therapeutic dose established
anti-factor Xa heparin assay
antithrombin binding to Xa is increased in pts receiving heparin - directly measures heparin activity
0.3-0.7 therapeutic range for anticoagulation with unfractionated heparin
warfarin
vitamin k antagonist - factors VII, IX, X and prothrombin
long 1/2 life, delayed onset because doesn’t degrade already circulating factors
indicated for long-term prophylaxis/treatment of venous &arterial thrombosis/PE. Prevention of thrombosis with aFib,
interactions. -many d-d
promote bleeding - heparins, ASA and nonASA antiplatelets
dec effect - seizure meds - carbamezapine, phenytoin, OCP, rifampin
inc effect - azoles, cimetidine, amiodarone
dietary vitamin K
PT nl= 12 seconds
target INR of 2-3 for MI,Afib (normal 0.8-1.2)
mechanical heart valve - 3-4.5
heparin and warfarin together
coumadin delayed, heparin immediate
if on heparin drip, expect to start warfarin at about the same time or anytime during transition
When INR is w/in therapeutic anticoagulant range, heparin d/ced
dabigatron
Direct Thrombin Inhibitor
aka direct oral anticoagulants
prevents the conversion of fibrinogen to fibrin/activation of factor VIII
oral - do not chew/crush
advantages over warfarin -rapid onset, fixed dosage, infrrequent coag testing, few d-d interactions, lower risk of hemorrhagic stroke/major bleeds
indic: prevent clots - DVT, PE afib, surgery
ADR:
bleeding (lower risk than warfarin)
GI disturbances (dyspepsia, ulceration, gastritis, etc)
limited clinical experience
no antidote
argatroban
continuos IV direct thrombin inhibitor - prophylaxis and treatment of thrombosis in patients with HIT
allergic rxns in combo w/ thrombolytics (alteplase) and contrast media
Rivaroxaban (Xarelto) , Apixaban (eliquis)
Oral anticoagulants
Factor Xa inhibitors
NOACs - novel oral anticoagulants
prevention DVT/PE - orthosurgery, treatment of DVT/PE unrelated to ortho, prevention of recurrent DVT/PE, prevention of stroke in afib
ADRs
less risk of bleeds compared to warfarin
spinal/epidural homatoma - hold 18 hrs post cath/OR
renal impairment, hepatic impairment (xeralto), pregnancy
d-d interactions - HIV antivirals, anti sz, anti-fungals
antidote - andexnet - life threatening bleeds
Aspirin (ASA)
antiplatelet
irreversible inhibition of cyclooxygenase (COX) required for synthesis of TXA2 - necessary to activate platelet, also promotes vasoconstriction on VSM
–> platelet aggregation and vasoconstriction inhibited
indic: ischemic stroke, TIA, chronic stable and unstable angina, primary prevention of MI (angina or hx of MI), Acute MI, bypass surgery, coronary stenting
ADR: bleeding, GI bleeding, hemorrhagic stroke
platelet altered irreversibly - double bleeding time for 7 days (life of platelet 7 days)
stop ASA 1 week prior to surgery
Clopidogrel (plavix)
antiplatelet
used alone or combo w/ ASA
prodrug - converted by CYP2C19
MOA: block p2y12 ADP receptor on platelet surface
prevents ADP stimulated platelet aggregation
indic: reduction clots in stents, prevent CVA and ACS, MI, effective in PAD
ADR: abdominal pain, dyspepsia, diarrhea and rash
bleeding (less than ASA)
stop med 5-7 days prior to surgery
TTP (thrombotic thrombocytopenic purpura) rare potentially fatal
d-d all other anticoags, and CYP2inhibitors, PPI (may reduce GI bleed by also clopidogrel effectiveness
+herbals - chamomile, clove, garlic, ginger, ginkgo, ginseng, anise
-poor metabolizers - genetic inability to convert to active form (blood/saliva tests)
Abcixamab
most effective antiplatelet - gpIIb/IIIa receptor antagonist (reversible)
“super aspirins”
used during PCI -pts experiencing ACS to prevent re-occlusion
antiplatelet effects 24-48 hrs after infusion stopped
used in combo with heparin and ASA
no ADRs mentioned
Alteplase
Thrombolytic - tPA
all thrombolytics are used in acute MI,
also used ischemic stroke, massive PE, v low dose to clear a vascular line
ADR- inc risk of hemorrhage
monitor for change in LOC, tarry stools, pink urine, swelling at joints, hold pressure on venipunctures/injections etc much longer than normal
no venipuncture or insertion of tubes after admin of drug - must do first
use early
positive symptoms
hallucinations, delusions, agitation, and paranoia
negative symptoms
lack of motivation, blunt affect, social withdrawal
cognitive symptoms
disordered thinking, memory and learning difficulties, inattentiveness
possible primary biologic deficit - schizophrenia
excessive activation of CNS receptors for dopamine
insufficient activation of CNS receptors for glutamate
drug selection based primarily on tolerability - side effect profiles rather than therapeutic effect - do not alter underlying pathology, treatment is not curative - provides sx relief
take 1-2 weeks to work, up to 4 weeks for full effect
positive sx may respond better
“Typical” First-generation antipsychotics
phenothiazines - low - chlorpromazine
high - fluphenazine
non-phenothiazines - med - loxapine
high - haloperidol
stronger block for dopamine in CNS
high risk for EPS
neuroleptic malignant syndrome -srs, rare - most with high potency FGA
other ADRs: orthostatic hypotension, sedation, neuroendocrine inc in prolactin (menstrual disorders, gynocomastia, promote malignancies)
seizures, sexual dysfunction, agranulocytosis, dbl mortility rate in pts with dementia, neonates - exposure/withdrawal
d-d
teach pt to avoid any CNS depressants - alcohol, antihistamines, benzodiazepines, barbiturates, THC
avoid - anticholinergic intensified - antihistamines, OTC sleep aids
Parkinsons meds - counteract effect of antipsychotic
neuroleptic malignant syndrome
srs, rare - most with high potency FGA - muscle rigidity, sudden high fever, AMS, seizures, tachy/dysrhythmias/arrest, rhabdomyolysis
–> requires immediate treatment - d/c med, cooling measures, treatment of rigidity - benzodiazepines, muscle relaxants
haloperidol
high potency, first-generation - non-phenothiazine
prolonged QT interval
used in tourrette’s syndrome, prevention of CINV, behavioral problems in children, agitation/aggression in pts w/ alchohol withdrawal,
chlorpromazine
low potency phenothiazine
prolonged QT interval
treatment of intractable hiccups
FGA adverse drug effects - block adrenergic receptors
hypotension, dizziness, drowsiness
FGA adverse drug effects - block muscarinic receptors
constipation, blurred vision, dry mouth
FGA adverse drug effects -block histamine type 1 receptors
drowsiness, sedation, antiemetic
FGA adverse drug effects - block dopamine 2 receptors - extrapyramidal symptoms
pseudo parkinsonian, acute dystonia (laryngeal spasms, grimacing, upward eye movement), akathisia (restlessness), tardive dyskinesia 15-20% on long-term therapy (protrusion, rolling tongue, sucking/smacking, chewing motion, involuntary movements - choreoathetoid - twisting, writhing, worm-like)
if tardive dyskinesia develops - irreversible, decrease anticholinergics, decrease dose FGA, admin benzodiazepines and switch to 2nd generation agent
“atypical” second-generation antipsychotics
moderate dopamine receptor blockade
stronger block of receptors for serotonin
lower risk for EPS
significant risk for metabolic effects - weight gain, new onset DM
other ADRs: seizures 3% of pts/dose related, myocarditis - rare, orthostatic hypotension, prolonged QT - check EKG at start, periodically, dysrhythmias, effect on older pts/dementia - dbl rate of mortality
teratogenic - xindic pregnancy/lactation
clozapine
olanzapine
quetiapine
risperidone
aripiprazone
clozapine
first SGA - often found to be most effective
greatest metabolic effects (along with olanzapine)
agranulocytosis- 1-2% of patients - mandatory monitoring
risperidone
SGA
Used for schiz, bipolar or autism - offlable for anxiety/agitation
commonly used in hospitals
has been shown to 2x risk stroke/death when used off-label (continuous)
neuroleptic malignant syndrome
suicidal ideation
monitor for metabolic effects, NMS, mood changes
depression
most common psych disorder, second behind HTN as most common chronic condition
10-20% of pop’n
only 35% of people are treated - underdxed, undertreated
charac’d by loss of pleasure, weight loss/gain, insomnia or excessive sleeping
caused by functional deficiency of monamine neurotransmitters - norepinephrine (alertness, concentration, energy), serotonin (obsessions,compulsions, memory), dopamine (pleasure/reward, motivation/drive)
or combination therein
treatment -psycho, somatic
pharmaco:
SSRIs
SNRIs
TCAs
MAOIs
atypical antidepressants
reactive depression
sudden onset - precipitating event
patient has known reason
can be treated with a benzodiazapine - short-term
major depressive
no identifiable cause
antidepressants effective
bipolar - types of depression
mood swings between manic and depressive
treated with “mood stabilizers”
monitoring - antidepressants
initial response 1-3 weeks
cannot be used PRN
should be used 4-8 weeks to assess efficacy - increase dose, switch med in same class, switch different class, add second drug
risk for suicide - especially early in treatment - applies to all populations but SI induced suicide especially in young people
monitor med counts - can be used in suicide
must be d/c’ed slowly over several weeks
abrupt w/d -HA, dizziness, tremors, nausea, palpitations, anxiety
first choice: SSRIs, SNRIs, Buproprion, Mirtazapine - tolerated
older + more ADRs: TCAs, MAOIs
ADRs - all antidepressants
Serotonin syndrome
rapid onset 2-72 hours
AMS, confusion
autonomic dysfunction: tachy, shivering, hypertension
neuromuscular: rigidity, tremors
risk inc using any 2 drugs that increase serotonin levels - SSRIs, MAOIs, TCAs, St. John’s Wart, Lithium
SSRIs
Fluoxetine (prozac) - long t1/2
Sertraline (zoloft)
Paroxetine (paxil)
Citalopram (celexa)
Escitalopram (lexapro)
Fluvoxamine (luvox)
“effective for sadness, panic, compulsion”
most commonly rxed antidepressant
indic: major depression, OCD, panic, social phobia, PTSD, GAD, anorexia
ADRs: sexual dysfunction, weight gain
*may result in noncompliance
insomnia, nervousness, anxiety, nausea
BBW - SI - early
Serotonin syndrome - stop MAOI 14 days before starting SSRI, 5 weeks between fluoxetine and MAOI
use concurrently is contraindicated
Caution in pregnancy r/t neonates - NAH, PPHN
SNRIs
Venlafaxine
Duloxetine
Desvenlafaxine
Levominacipran
similar therapeutic effect/ ADRs as SSRIs
may lead to HTN
TCAs
older, not used as frequently
block uptake of norepi and serotonin
amitriptyline
Imipramine
indic: depression, bipolar, fibromyalgia, neuropathic pain, migraine
ADRs- sedation, orthostatic hypotension, anticholinergic effects, diaphoresis, cardiac toxicity, seizures, hypomania, increased risk of suicide
MAOIs+TCAs can lead to hypertensive crisis
receptors blocked:
alpha1 –> orthostatic hypotension
histamine1 –> sedation
cholinergic/muscarinic–> anticholinergic effects
should not be combined with MAOI, anticholinergic, CNS depressants
should not be combined with SSRI, SNRI –> leads to ss
MAOI - monoamine oxidase inhibitors
inhibits the enzyme (found in brain, liver, intestine) that inactivates monoamine neurotrasnmitters NE, 5-HT, dopamine, tyramine (inhibits the metabolism of these)
inactivate both MAO-A (NE, 5-ht, tyramine) and MOA-B (dopamine)
do not inactivate tyramine - accumulates
isocarboxazid, tranylcypromine, phenelzine, selegiline (td patch)
equally effective, 2nd or 3rd line d/t ADRs - severe HTN when combined with tyramine foods, sympathomimetics
must not combine with SSRI, SNRI –> risk for ss
Selegiline
transdermal MAOI
also used for parkinson’s - oral - selective for MAO-B (dopamine)
when treating depression, higher blood levels –> non selective
risk for HTN crisis + tyramine foods lower with transdermal patch
Atypical antidepressants
reactive or major depression
MOA- unclear, may effect one of three neurotransmitters (S,N,D)
NDRI - buproprion (welbutrin) or Serotonin antagonist (mirtazapine, trazodone)
NDRI - buproprion
used for SAD, major depression
similar molecule to amphetamines - weight loss
thought to block norepi and dopamine reuptake, mechanism unclear
does not affect serotonin, cholinergic, histamine receptors
appears to increase sexual desire/pleasure
also used for smoking cessation
Mirtazapine, Remeron - serotonin antagonist
increase release of serotonin and NE
also blocks histamine receptors - sedation + weight gain
generally well tolerated, somnolence common, avoid CNS depressants
St. John’s Wart
naturally reduces reuptake of the three neurotransmitters
mild to moderate depression
OTC
risk for serotonin syndrome
liver enzyme inducer
mood stabilizers
llithium
AEDs:
Valproate
Carbamazepine
Lamictal
lithium
salt substitute
MOA unclear
narrow therapeutic range (0.5-1.0 mEq/L) - monitor serum lithium (every 1-3 days at start therapy)
ADRs:
dry mouth, thirst, increased urination (ant. ADH), weight gain, peripheral edema, metallic taste
excreted by kidneys - decreased when low blood Na
risk for toxicity inc with low Na
levels 1.0 -1.5
nausea, vomiting, anorexia, polyuria, thirst, slurred speech, fine tremors
levels 1.5-2.0
persistent GI upset, hand tremors, confusion, muscle hyperirritability, ECG changes, sedation
levels 2.0-2.5
ataxia, high UOP, serious ECG changes, tinnitus, hypotension, clonus, seizures
above 2.5
convulsions, oliguria, death
d-d
diuretics - Na loss
ACE inhibitors - inc risk for toxicity
NSAIDs: increase renal reabsorption of lithium (rise in lithium)
anticholinergics - cause urinary hesitancy
AEDs:
Valproate
Carbamazepine
Lamictal
antiepileptic drugs
proven to be effective mood stabilizers - not quite as effective at preventing depressive episodes
V - replaced lithium as drug of choice for many pts (wider therapeutic index, less ADRs)
Amphetamine/amphetamine-like drugs
ADHD drug of choice
CNS stimulants
response can diminish after 2-3 years (time for behavioral therapy)
impulsiveness/hyperactivity may decrease
does not reduce negative behaviors
ADRs: insomnia, growth suppression, weight loss
avoid caffeine
take medication early in day, dosing to minimize interference with mealtimes
dependence - periodic drug free holidays
diversion common
OD - treat with increased acidity of urine - decreases the t1/2
Methylphenidate (ritalin)
most common drug rx’ed to kids
CNS accelerant
short duration - ritalin
sustained release - SR, Quilivant (oral suspension)
long duration - concerta, daytrana - should be removed 9-10/day(transdermal patch)
second line drugs - ADHD
less effective than stimulants
atomoxetine
guanfacine
clonidine
no potential for abuse
BBW - inc risk for SI
may increase BP, HR
may cause appetite suppression - minimal effects on growth
atomoxetine
second line ADHD drug
norepinephrine reuptake inhibitor
admin 1/day
no potential for abuse
BBW - inc risk for SI
may increase BP, HR
may cause appetite suppression - minimal effects on growth
guanfacine
clonidine
alpha 2 adrenergic agonists - unknown MOA for ADHD
both og approval for HTN
ADRs: somnolence, weight gain, reduced BP
