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Thrombolytics and MH Flashcards

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1
Q

stage 1 hemostasis - formation of platelet plug

A

activation of GP IIb/IIIa - fibrinogen bridges, platelet aggregation

stimulated by thromboxane A, thrombin, collagen, platelet activation factor, ADP

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2
Q

Stage 2 hemostasis - coagulation

A

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

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3
Q

prevention of arterial thrombosis

A

Antiplatelet medication - prevents platelets from
clumping together to form a clot
damage often local

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4
Q

prevention of venous thrombosis

A

anticoagulants - disrupt coagulation cascade
damage is distant

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5
Q

anticoagulants contraindications/heparin

A

x-id - with risk for bleeding active hemorrhage, recent hemorrhagic stroke, active lumbar puncture, surgery on eye, brain, spinal cord, thrombocytopenia

extreme caution: dissecting aneurysm, severe hypertension, hemophilia, recent (3mo) surgery, pregnancy, very recent abortion/miscarriage, recent GI bleed - PUD

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6
Q

Thrombolytics

A

“clot busters” - break up existing clot by speeding up conversion of plasminogen to plasmin

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7
Q

Anticoagulants

A

Prevent venous thrombosis

Heparin and derivatives
vitamin K antagonists - Warfarin
Direct Thrombin inhibitors
Factor Xa inhibitors

low dose=prophylactic dose
full dose=therapeutic dose/treatment dose

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8
Q

Heparin

A

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

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9
Q

anticoagulant (heparin) use - risk of spinal/ hematoma

A

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

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10
Q

heparin antidote

A

protamine sulfate

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11
Q

Normal platelet values

A

> 150,000
check for pts on heparin in addition to aPTT

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12
Q

INR

A

mechanical valve – 3-4,
Afib – 2-3
normal

check for pts on warfarin
always done with PT (prothrombin time)

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13
Q

natural fibinolysis

A

destruction of clot via tissue plasminogen activator (tPA) - converts inactive plasminogen to active enzyme plasmin
plasmin degrades fibrin mesh and breaks up clot

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14
Q

natural fibinolysis

A

destruction of clot via tissue plasminogen activator (tPA) - converts inactive plasminogen to active enzyme plasmin
plasmin degrades fibrin mesh and breaks up clot

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15
Q

suspect HIT

A

-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

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16
Q

aPTT - activated partial thromboplastin time

A

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

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17
Q

anti-factor Xa heparin assay

A

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

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18
Q

warfarin

A

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

antidote = vitamin K

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19
Q

heparin and warfarin together

A

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

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20
Q

dabigatron

A

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

Monitoring: Infrequent aPTT; check LFTs

ADR:
bleeding (lower risk than warfarin)
GI disturbances (dyspepsia, ulceration, gastritis, etc)
limited clinical experience

antidote: idarucizumab

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21
Q

argatroban

A

continuos IV direct thrombin inhibitor - prophylaxis and treatment of thrombosis in patients with HIT
allergic rxns in combo w/ thrombolytics (alteplase) and contrast media

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22
Q

Rivaroxaban (Xarelto) , Apixaban (eliquis)

A

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

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23
Q

Aspirin (ASA)

A

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

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24
Q

Clopidogrel (plavix)

A

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 effectiveness)
+herbals - chamomile, clove, garlic, ginger, ginkgo, ginseng, anise

-poor metabolizers - genetic inability to convert to active form (blood/saliva tests)

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25
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
26
Alteplase
Thrombolytic - tPA or tissue plasminogen activator 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, intracranial bleed monitor for change in LOC, tarry stools, pink urine, swelling at joints, hold pressure on venipunctures/injections etc much longer than normal If bleeding cannot be controlled- iv aminocaproic acid - inhibits plasmin no venipuncture or insertion of tubes after admin of drug - must do first use early Advantage - does not cause allergic rxns or hypotension
27
positive symptoms
hallucinations, delusions, agitation, and paranoia
28
negative symptoms
lack of motivation, blunt affect, social withdrawal
29
cognitive symptoms
disordered thinking, memory and learning difficulties, inattentiveness
30
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
31
"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
32
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
33
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,
34
chlorpromazine
low potency phenothiazine prolonged QT interval treatment of intractable hiccups
35
FGA adverse drug effects - block adrenergic receptors
hypotension, dizziness, drowsiness
36
FGA adverse drug effects - block muscarinic receptors
constipation, blurred vision, dry mouth
37
FGA adverse drug effects -block histamine type 1 receptors
drowsiness, sedation, antiemetic
38
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
39
"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
40
clozapine
first SGA - often found to be most effective greatest metabolic effects (along with olanzapine) agranulocytosis- 1-2% of patients - mandatory monitoring
41
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
42
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
43
reactive depression
sudden onset - precipitating event patient has known reason can be treated with a benzodiazapine - short-term
44
major depressive
no identifiable cause antidepressants effective
45
bipolar - types of depression
mood swings between manic and depressive treated with "mood stabilizers"
46
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
47
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
48
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
49
SNRIs
Venlafaxine Duloxetine Desvenlafaxine Levominacipran similar therapeutic effect/ ADRs as SSRIs may lead to HTN
50
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
51
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
52
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
53
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)
54
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
55
Mirtazapine, Remeron - serotonin antagonist Atypical antidepressants
increase release of serotonin and NE also blocks histamine receptors - sedation + weight gain generally well tolerated, somnolence common, avoid CNS depressants
56
St. John's Wart
naturally reduces reuptake of the three neurotransmitters mild to moderate depression OTC risk for serotonin syndrome liver enzyme inducer
57
mood stabilizers
llithium AEDs: Valproate Carbamazepine Lamictal
58
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
59
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)
60
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
61
Methylphenidate (ritalin)
most common drug rx'ed to kids for ADHD CNS accelerant short duration - ritalin sustained release - SR, Quilivant (oral suspension) long duration - concerta, daytrana - should be removed 9-10/day(transdermal patch)
62
second line drugs - ADHD
less effective than stimulants, sometimes used as adjuncts atomoxetine guanfacine clonidine
63
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
64
guanfacine clonidine
alpha 2 adrenergic agonists - unknown MOA for ADHD both og approval for HTN ADRs: somnolence, weight gain, reduced BP

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