Thrombolytics and MH

Question 1

stage 1 hemostasis - formation of platelet plug

Answer 1

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

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

Question 2

Stage 2 hemostasis - coagulation

Answer 2

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

Question 3

prevention of arterial thrombosis

Answer 3

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

Question 4

prevention of venous thrombosis

Answer 4

anticoagulants - disrupt coagulation cascade
damage is distant

Question 5

anticoagulants contraindications/heparin

Answer 5

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

Question 6

Thrombolytics

Answer 6

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

Question 7

Anticoagulants

Answer 7

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

Question 8

Heparin

Answer 8

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

Question 9

anticoagulant (heparin) use - risk of spinal/ hematoma

Answer 9

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

Question 10

heparin antidote

Answer 10

protamine sulfate

Question 11

Normal platelet values

Answer 11

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

Question 12

INR

Answer 12

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

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

Question 13

natural fibinolysis

Answer 13

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

Question 14

natural fibinolysis

Answer 14

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

Question 15

suspect HIT

Answer 15

-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

Question 16

aPTT - activated partial thromboplastin time

Answer 16

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

Question 17

anti-factor Xa heparin assay

Answer 17

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

Question 18

warfarin

Answer 18

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

Question 19

heparin and warfarin together

Answer 19

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

Question 20

dabigatron

Answer 20

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

Question 21

argatroban

Answer 21

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

Question 22

Rivaroxaban (Xarelto) , Apixaban (eliquis)

Answer 22

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

Question 23

Aspirin (ASA)

Answer 23

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

Question 24

Clopidogrel (plavix)

Answer 24

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)

Question 25

Abcixamab

Answer 25

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

Question 26

Alteplase

Answer 26

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

Question 27

positive symptoms

Answer 27

hallucinations, delusions, agitation, and paranoia

Question 28

negative symptoms

Answer 28

lack of motivation, blunt affect, social withdrawal

Question 29

cognitive symptoms

Answer 29

disordered thinking, memory and learning difficulties, inattentiveness

Question 30

possible primary biologic deficit - schizophrenia

Answer 30

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

Question 31

“Typical” First-generation antipsychotics

Answer 31

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

Question 32

neuroleptic malignant syndrome

Answer 32

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

Question 33

haloperidol

Answer 33

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,

Question 34

chlorpromazine

Answer 34

low potency phenothiazine
prolonged QT interval
treatment of intractable hiccups

Question 35

FGA adverse drug effects - block adrenergic receptors

Answer 35

hypotension, dizziness, drowsiness

Question 36

FGA adverse drug effects - block muscarinic receptors

Answer 36

constipation, blurred vision, dry mouth

Question 37

FGA adverse drug effects -block histamine type 1 receptors

Answer 37

drowsiness, sedation, antiemetic

Question 38

FGA adverse drug effects - block dopamine 2 receptors - extrapyramidal symptoms

Answer 38

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

Question 39

“atypical” second-generation antipsychotics

Answer 39

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

Question 40

clozapine

Answer 40

first SGA - often found to be most effective
greatest metabolic effects (along with olanzapine)
agranulocytosis- 1-2% of patients - mandatory monitoring

Question 41

risperidone

Answer 41

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

Question 42

depression

Answer 42

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

Question 43

reactive depression

Answer 43

sudden onset - precipitating event
patient has known reason
can be treated with a benzodiazapine - short-term

Question 44

major depressive

Answer 44

no identifiable cause
antidepressants effective

Question 45

bipolar - types of depression

Answer 45

mood swings between manic and depressive
treated with “mood stabilizers”

Question 46

monitoring - antidepressants

Answer 46

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

Question 47

ADRs - all antidepressants Serotonin syndrome

Answer 47

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

Question 48

SSRIs

Answer 48

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

Question 49

SNRIs

Answer 49

Venlafaxine
Duloxetine
Desvenlafaxine
Levominacipran

similar therapeutic effect/ ADRs as SSRIs
may lead to HTN

Question 50

TCAs

Answer 50

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

Question 51

MAOI - monoamine oxidase inhibitors

Answer 51

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

Question 52

Selegiline

Answer 52

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

Question 53

Atypical antidepressants

Answer 53

reactive or major depression
MOA- unclear, may effect one of three neurotransmitters (S,N,D)
NDRI - buproprion (welbutrin) or Serotonin antagonist (mirtazapine, trazodone)

Question 54

NDRI - buproprion

Answer 54

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

Question 55

Mirtazapine, Remeron - serotonin antagonist
Atypical antidepressants

Answer 55

increase release of serotonin and NE
also blocks histamine receptors - sedation + weight gain
generally well tolerated, somnolence common, avoid CNS depressants

Question 56

St. John’s Wart

Answer 56

naturally reduces reuptake of the three neurotransmitters
mild to moderate depression
OTC
risk for serotonin syndrome
liver enzyme inducer

Question 57

mood stabilizers

Answer 57

llithium
AEDs:
Valproate
Carbamazepine
Lamictal

Question 58

lithium

Answer 58

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

Question 59

AEDs:
Valproate
Carbamazepine
Lamictal

Answer 59

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)

Question 60

Amphetamine/amphetamine-like drugs

Answer 60

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

Question 61

Methylphenidate (ritalin)

Answer 61

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)

Question 62

second line drugs - ADHD

Answer 62

less effective than stimulants, sometimes used as adjuncts

atomoxetine
guanfacine
clonidine

Question 63

atomoxetine

Answer 63

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

Question 64

guanfacine
clonidine

Answer 64

alpha 2 adrenergic agonists - unknown MOA for ADHD

both og approval for HTN

ADRs: somnolence, weight gain, reduced BP