Pharmacology Exam 6

Antiplatelets

used to reduce aggregation properties of platelets

Aspirin

ADP receptor blockers

Glycoprotein IIb/IIIa receptor blockers

Thrombolytics

Dissolve existing clots in patients patients with MI or Stroke (fibrinolysis)

alteplase

streptokinase

tenecteplase

narrow margin of safety, risk of bleed might outweigh therapeutic benefit esp. 75+

pathophysiology of MI

a blood clot blocks the coronary artery 100% causing prolonged ischemia

primary cause is ruptured plaque

severe CP primary symptom

clotting cascade 4 steps (hemostasis process)

1. vasoconstriction as a reflex to injury

2. platelet aggregation at site of injury: platelets activated by ADP, thrombin, thromboxane A2

3. Fibrinigen converted to fibrin creatinging a soft plug with the platelets

4. plug gets help with other factors to become a thrombus

   1. healing stage: plasmin breaks up fibrin (process of fibrinolysis) to allow blood flow to get back to normal

Anticoagulation

prevent clot formation and growth

Heparin

T: anticoagulant

P: indirect thrombin inhibitor

INDICATION: DVT, PE, unstable angina, evolving MI, prevention of thrombosis in high risk pt

drug of choice to treat thromboembolic disease

MOA: binds to antithrombin III, which inhibits thrombin and inactivates factor Xa

-prolongs coagulation time, thereby inhibiting excessive clotting within blood vessels.

-prevents enlargement of existing clots and formation of new ones but does NOT dissolve existing ones

AE: abnormal bleeding (10% higher dose=higher risk)) osteoporosis, hypersensitivity, hematoma

BLACK BOX: epidural or spinal hematoma when getting lumbar puncture or anesthesia = paralysis

-Heparin induced thrombocytopenia (30%)

CONTRA: internal bleeding , HTN, recent trauma, intracranial hemorrhage

OKAY for PREG

SQ abd

Heparin induced thrombocytopenia

platelet count falls but increased risk for blood clots. Body creates an antibodies that make platelet clump but also decreases amount of platelets circulating

Enoxaparin

Low molecular weight heparin

more predictable (do not monitor aPTT) becuse less binds to proteins

binds only to Factor Xa so less likely thrombocytopenia

SQ abd

Warfarin

T:anticoagulation

P: Vitamin K antagonist

INDICATION: prophylaxis of arterial thromboembolism, Stroke-TIA, MI, A-Fib, TX and prevention of DVT/PE in surgery pts, prosthetic/mechanical heart valve

MOA:Inhibits two enzymes involved in formation of activated Vitamin K(required for synthesis of clotting factors)

-inhibits synthesis of new clotting factors but not already circulating ones

AE: Abnormal bleeding, systemic microembolization, osteoperosis, purple toe syndrome

BLACK BOX: NO for PREG fatal

CONTRA: recent trauma, HTN, active internal bleeding, intracranial hemorrhage, hepatic impairment

has long half life so takes 3-4 days to reach therapeutic effect and 3-4 days after stopping for body to make new clotting factor

Dabigatran

T: anticoagulant

P:direct thrombin inhibitor

INDICATION:stroke prophylaxis, with nonvascular AFib, DVT,PE

MOA: directly inhibits the action of thrombin by binding to it

AE: bleeding, abrupt discontinuation = inc risk for thrombotic event

CONTRA: active bleeding, mechanical heart valves, severe kidney disease

-as effective as warfarin but no lab monitoring needed

Acetylsalicylic acid (Aspirin)

T: Anti-platelet, (analgesic, antipyretic )

P: NSAID, Salicylate

INDICATION: MI prophylaxis, suspected coronary thrombosis PTA

MOA:binds to COX enzyme in platelets, inhibiting aggregation

AE: Anaphylaxis, stomach irritation/pain, GI bleed, thrombocytopenia, hemolytic anemia, tinnitus, hearing loss (high dose)

CONTRA: chronic rhinitis, ICP, GI bleed Hx, HF, children, ulcer prone

Clopidogrel

T:Anti-platelet

P: ADP Receptor blocker

INDICATION: prophylaxis for arterial thromboembolism, stroke, MI

MOA: block ADP on platelets (ADP needed to promote aggregation)

AE: bleeding, same tolerability as aspirin

BLACK BOX: poor metabolizers may not see benefit (prodrug)

Depends on good CYP450 enzymes for metabolism

platelet fxn inhibition can last several days after DC

Abciximab

T: antiplatelet

P: Glycoprotein IIb/IIIa inhibitor

INDICATION: coronary angioplasty procedures, revascularization of arteries

MOA: binds to GP IIb and IIIa receptor sites on platelets which prevents fibrinogen, von willebrand factor and other procoagulants

AE: abnormal bleeding at access site

only given IV

Alteplase (tPA)

T: drug tat dissolves blood clots

P: thrombolytic/fibrinolytic

INDICATION: MI, PE,ischemic stroke, clotted central lines

MOA: converts plasminogen to plasmin- dissolves fibrin clots

AE: bleeding

CONTRA: ICH, known structural cerebral vascular lesion, intracranial neoplasm, ischemic stroke <3mo, AAA, active bleeding

Aminocaproic Acid

T: antifibrinolytic (HELPS BLOOD CLOT)

P: Hemostatic

USE: treat excessive hemorrhage; surgery

MOA: blocks sites on plasminogen and plasmin which prevents digestion of fibrin clot

AE: thrombosis, rhabdomyolysis (rare)

How do NSAIDS damage GI mucosa

prostaglandins provide GI protecting by increasing bicarbonate and mucus production to protect stomach mucosa from acid.

NSAIDs inhibit COX in the stomach removing prostiglandin’s protective effects, increasing ulcer risk

Ibuprofen

T: anti-inflammatory, antipyretic, analgesic

P: NSAID

INDICATION: arthritis, headache, mm pain, dental pain, dysmenorrhea

MOA: COX-1 COX-2 inhibition, blocks prostaglandin synthesis

AE: GI (most common):bleeding, anorexia, heartburn, N/V/D/C; Adverse CNS: HA, dizziness, drowsy, tinnitus

BLACK BOX: thrombotic cardiac events, MI, stroke

CONTRA: allergy, ASA other NSAIDS, bleeding abnormalities, not for open heart post op, PREG

INTERACTIONS: blood thinners,

Celecoxib

T: anti-inflammatory, antipyretic, analgesic

P: COX 2 inhibitor, NSAID

INDICATION: mild to moderate pain, arthritis, HA

MOA:selectively inhibits COX 2, inhibits pg synthesis and reduces inflammation

AE: HA, Fever, HTN, Dizziness, insomnia

BLACK BOX:cardiac events

INTERACTIONS: anticoags, GI with ETOH, steroids, ASA, other NSAIDS, NO PREG

acetaminophen

T:nonopioidanalgesic, antipyretic

P: Para-aminophenol derivative

INDICATION: pain, fever (hypothalmus), HA, dysmenorrhea, arthritis

MOA: inhibits COX in CNS (no effect on platelets)

AE: rare if used as directed : leukopenia, neutropenia, anemia

BLACKBOX:liver damage, allergic rxn, angioedema

Interaction: Alcohol = inc liver damage

OK pregnancy

NOT FOR INFLAMMATION

Aspirin for inflammation

MOA: inhibition of COX 1 and COX 2 enzymes which reduces PG synthesis

How do muscle relaxers relieve pain

work at brainstem and spinal cord levels. Increases norepi activity by blocking its synaptic reuptake to produce an anticholinergic effect

cyclobenzaprine

T: skeletal muscle relaxant

P: centrally acting

INDICATION: skeletal muscle relaxant short term use for spasms and joint mobility problems

MOA: acts at the brain stem and spinal cord level to increase norepi activity by blocking its synaptic reuptake

AE: drowsiness, xerostomia, dizziness, fatigue, nausea, some anti depressant effects

CONTRA": alcohol, opioids, barbituates, CNS depressant

what are corticosteroids and how they work

mimic cortisol (natural hormone made by adrenal glands)

cortisol supresses immunesystem and reduces joint, pain, swelling, and heat

Hydrocortisone

T: adrenal hormone; antinflammatory

P corticosteroid

INDICATION: arthritis pain, inflammatory conditions, allergies, autoimmune disorder, sever inflammation

MOA: anti-inflammatory, blocks immune response and inhibits synthesis of inflammatory mediators (PG, histamine, kinin)

Asessmenta nd classification of pain

Assess: location, intensity, quality, precipitating/relieving factors

pain scale

Classification: acute or chronic

Nonpharmacologic TX

RICE

heat/cold

PT

mediation

yoga

distraction

acupuncture

accupressure

Pharmacologic TX of pain

NSAIDS, nonopioids, acetaminophen, opioids, adjuvant analgesia

Morphine sulfate

T: narcotic analgesic

P: opioid agonist

INDICATIONS: severe pain

MOA: occupies Mu and Kappareceptor sites in brain and spinalcord that alter release of afferent neurotransmitters

AE: CNS depression-sedation, euphoria, disorientation, respiratory depression, constipation, N/V, peripheral vasodilation

BLACKK BOX: schedule II controlled substance high potential for dependence

INTERACTIONS: CNS depressants,skeletal mm, relaxants, ETOH MOIs alll increase sedtaion

Tramadol

Mixd opioid-nonopioid agonist

INDICATION": moderate pain that needs around te clock anesthesia

MOA: opioids binds to Mu and inhibits norepi and seretonin reuptake in spinal neurons which inhibit transmission of pain impulses

AE: vertigo, dizzines, constipation N/V, tremor, anxiety, confusion, lower sz threshold

CONTRA: depression hx, suicidal, ETOH, CNS Depressants, <12yo

sumatriptan

serotonin (5-HT) receptor agonist

INDICATION: acute migrane HA

MOA: vasoconstriction action in blood vessels in and around brain and reducing the pain signal transmission

AE” dizziness, nausea, reoccurence HA, cardiac events

CONTRA: CVD,PVD, HTN, family hx of CVD,CKD, hepatic impairment, increase sz with epilepsy pt