Download clots

Vascular
Perfusion:
Drugs Affecting
Coagulation
Clotting
• The process in which blood is converted
to a semi-solid gel.
• When clotting doesn’t occur patients are
at risk for bleeding.
• When too much clotting occurs blood
flow can be obstructed to major
organs.
Physiology of Coagulation
• Blood circulates freely through large and
small blood vessels.
• Vessels must be able to form clots to
prevent excessive blood loss from injuries.
• Blood is composed of various cells and
substances, each assisting in maintaining a
balance of coagulation and anticoagulation.
Physiology of Coagulation
• The coagulation cascade is initiated by tissue
damage and platelet activation, which mobilize
the clotting factors circulating in the blood.
• The clotting cascade occurs over two pathways,
intrinsic and extrinsic.
Physiology of Blood Clotting
Blood Clotting Video:
http://www.youtube.com/watch?v=-bZUeb83uU&list=PLDDDE4C372FAB6A37&index
=3
Risk Factors for Clotting Disorders
•
•
•
•
Age
Genetics
Immobility
Smoking
Why?
Pathophysiology of Coagulation
Excessive clotting
– Deep Vein Thrombosis (DVT)
– Polycythemia (excess RBCs)
– Atrial fibrillation
Defective clotting
– Hemophilia
• Von Willebrand’s disease
– Thrombocytopenia
Pathophysiology
• When blood flow is impeded or slowed in an
area, coagulation occurs, leading to formation of
a thrombus (clot):
• Thrombi are the most common cause of:
– Myocardial infarction
– Cerebrovascular Accident (CVA) or “stroke”
– Limb gangrene (deep vein thrombosis, DVT)
• Turbulence of blood flow is the major cause of
embolization, or movement of a thrombus.
Deep Vein
Thrombosis
• A blood clot in one or more of the deep veins,
usually in the legs.
• May cause leg pain or may occur without
symptoms
Clinical Manifestations of a DVT
• Unilateral leg edema
• Extremity pain
• Feeling of fullness in
thigh or calf
• Paresthesia
• Warm skin
• Erythema
• Temperature
• Positive Homan’s
sign:
https://www.youtube.
com/watch?v=ac_om5
HCjvg
Prevention of DVT’s
• Patient on bed rest should
change positions
frequently.
• Early and aggressive
mobilization.
• Compression stockings
• Sequential compression
devices
• Drug therapy
(anticoagulants)
The Function of Vitamin K*
• Vitamin K is a group of fat soluble vitamins
required for blood coagulation
• Normal bacteria in the large intestine convert
Vitamin K from food to its activated form.
• Vitamin K1 is obtained primarily through the
consumption of green leafy vegetables (e.g.,
kale, spinach, romaine lettuce, broccoli, cabbage)
• Vitamin K2 is also obtained through the
consumption of aged cheeses, eggs and meats
*Koagulations-vitamin (Henrik Dam, 1929)
Anticoagulation Drugs
• Anticoagulants interfere with the clotting cascade
and prolong blood clotting time.
• Parenteral anticoagulants work by preventing the
conversion of fibrinogen to fibrin (Heparin).
• Oral anticoagulants work by preventing the
synthesis of factors dependent on vitamin K for
synthesis (Warfarin).
Prototype: Heparin
Prototype: Warfarin (Coumadin)
Heparin
• Pharmacotherapeutics
– Parenteral anticoagulant. It interferes with
the final steps of the clotting cascade.
• Pharmacokinetics
– Route: IV or SC. Never orally.
• Pharmacodynamics
– Rapidly promotes the inactivation of factor X,
which, in turn, prevents the conversion of
prothrombin to thrombin.
Heparin
• Side effects
– Bleeding
• Adverse effects
– Thrombocytopenia: a condition in which you
have an excessively low blood platelet count.
• Maximizing therapeutic effects
– Monitor laboratory values: activated Partial
Thromboplastin Time (aPTT) is measured.
Antidote for Heparin
• Protamine sulfate is the antidote for too much heparin.
Protamine sulfate was originally manufactured from the
sperm of Salmon fish but is now mostly synthetic.
• When administered alone, protamine has an anticoagulant
effect. However, when it is given in the presence of heparin,
a stable salt is formed which results in the loss of
anticoagulant activity of both drugs.
• Protamine sulfate has a rapid onset of action. Neutralization
of heparin occurs within five minutes after intravenous
administration.
• Protamine has been reported to cause allergic reactions in
patients who are allergic to fish.
Warfarin
• Pharmacotherapeutics
– Used as prevention (prophylactically) for
patients with a long-term risk for thrombus
formation
• Pharmacokinetics
– Administered: oral. Highly protein bound.
• Pharmacodynamics
– Competitively blocks vitamin K at its sites of
action
Warfarin
• Contraindications and precautions
– Active bleeding or bleeding disorders
• Side effects
– Bleeding
• Adverse effects
– Hemorrhage
• Drug interactions
– Several drug–drug and drug–food interactions
Warfarin
• Maximizing therapeutic effects
– Warfarin dosage should be individualized until
prothrombin time (PT) or international
normalized ratio (INR) is in therapeutic range.
• Minimizing adverse effects
– Assess the patient’s response to warfarin therapy.
– Minimize foods high in Vitamin K.
– Antidote to excessive bleeding is IM Vitamin K
Match Lab Test to Anticoagulant
• Heparin
?
• Warfarin
?
Match Lab Test to Anticoagulant
• Heparin
aPTT
Activated Partial
Thromboplastin Time
• Warfarin
PT, INR
Prothrombin Time
International Normalized
Ratio
Antiplatelet Drugs
• Used when overactive platelets pose long-term
risks for hypercoagulability.
• Platelet aggregation is important in hemostasis.
• Antiplatelet drugs reduce platelet aggregation.
• Antiplatelet drugs differ in their modes of action
and adverse effects.
Prototype: clopidogrel (Plavix)
Clopidogrel
• Pharmacotherapeutics
– Used to reduce atherosclerotic events
• Pharmacokinetics
– Administered: oral. Protein bound
• Pharmacodynamics
– Inhibits the binding of adenosine diphosphate (ADP)
to its platelet receptor and the subsequent ADPmediated activation of the glycoprotein IIb/IIIa
complex (part of the coagulation cascade) and thus
inhibits platelet aggregation
Clopidogrel
• Side effects
– Bleeding
– GI distress
• Adverse effects
– Neutropenia: Low neutrophils, a white blood cell
• Minimizing adverse effects
– Take clopidogrel with food to decrease GI problems.
– Severe neutropenia (low neutrophils, a white blood
cell) is a potential risk.
Enoxaparin (Lovenox)
• Pharmacotherapeutics
– Used to treat or prevent deep vein thrombosis
• Pharmacokinetics
– Absorbed IV or SubQ (not oral). Metabolized by liver.
T-1/2 4-5 hours
• Pharmacodynamics
– Is a type of low molecular weight Heparin
– Works by binding to antithrombin (a circulating
anticoagulant) to form a complex that irreversibly
inactivates clotting factor Xa.
Enoxaparin (Lovenox)
• Side effects
– Bleeding, Bruising at injection site
– Nausea, diarrhea
• Adverse effects
– Numbness, confusion, dizziness, weakness
• Minimizing adverse effects
– May be preserved in benzyl alcohol, which can
affect a fetus or cause reactions in susceptible
persons
– Avoid use of other anticoagulants
Thrombolytic Drugs
• Assist in breaking down already formed blood clots.
• Used for evolving, acute MI, a pulmonary emboli, or
acute ischemic (not hemorrhagic) stroke & to unclog
central venous catheters.
• May be given systemically or directly at the site of the
blood clot.
• Although these drugs are given during emergency
situations and can save lives, their adverse effects can be
life threatening.
Prototype: Alteplase (tPA)
Alteplase: Core Drug Knowledge
• Pharmacotherapeutics
– Thromboembolic conditions
• Pharmacokinetics
– Administered: IV. Rapidly cleared from the plasma
– Must give within 4 hours of onset of stroke
• Pharmacodynamics
– Acts in the same way as endogenous tPA
– Converts plasminogen to plasmin
Alteplase: Planning and Interventions
• Side or Adverse effects
– Internal or superficial bleeding
• Drug interactions
– Interacts with anticoagulants and antiplatelet drugs
• Minimizing adverse effects
– Closely and continually monitor vital signs and
observe for signs of active bleeding
– The patient should be connected to a cardiac
monitor, both during the treatment and afterward.
Pathophysiology – Deficient Clotting
• When clotting factors are deficient, blood
clotting does not occur in a timely
manner.
• A minor injury or trauma can cause
prolonged bleeding.
• Inherited deficiencies of specific clotting
factors produce hemophilic conditions.
Hemophilia: Pathophysiology
• Deficiency of antihemophilic factor (AHF) (also
called Factor VIII).
• Produced by the liver and is required to form
thromboplastin.
• Quantity of AHF determines severity of the
disease.
• People with hemophilia only have 2 of the 3
factors needed for clotting.
Types of Hemophilia
Bleeding disorders where there is a deficiency of
one the of the factors necessary for clotting.
• Genetic (X-linked recessive)
• Factor VIII deficiency
• Factor IX deficiency
• Von Willebrand disease
Clinical Manifestations of Hemophilia
• Prolonged bleeding
• Hemorrhage from
trauma
• Excessive bruising
• Subcutaneous &
intramuscular
hemorrhages
• Hemoarthrosis
(bleeding into joint
cavities)
• Hematomas
• Spontaneous
hematuria (blood in
the urine)
Clotting Factors
• Deficiencies of normal blood clotting factors
are associated with prolonged bleeding and
clot formation times.
• These deficiencies result from an inherited
absence of the factor.
• Replacement of these factors with clotting
factors is the treatment of choice.
Prototype: antihemophilic factor (AHF)
Exam 3:
Brief Medication Review
Upper Respiratory
Medication
Pharmacotherapeutics
Pharmacodynamics
Main Side or Adverse
Effects
Dextromethorphan
(Robitussin)
Cough
Suppressant
Works in the Central
Nervous System to reduce
desire to cough
Drowsiness
Don’t use with illnesses
where you need to cough
Guaifenesin
Expectorant
Liquifies secretions to
make them easier excrete
Drowsiness
Phenylephrine
(Neo-synephrine)
Decongestant
Sympathetic N.S.
Vasoconstriction in the
sinus cavities
Rebound congestion with
ongoing use
Pseudoephedrine
(Sudafed)
Decongestant
Sympathetic N.S.
Vasoconstriction in the
sinus cavities
Excitability, insomnia,
restlessness
Loratidine (Claritin)
Allergies
Antihistaminergic. Reduces Drowsiness
inflammation
Mometasone
(Nasonex)
Allergies
Nasal corticosteroid.
Reduces inflammation
Nose bleeds. Not for PRN
use
Lower Respiratory
Medication
Pharmacotherapeutics
Pharmacodynamics
Main Side or Adverse
Effects
Acetylcysteine
(Mucomyst)
Nebulized
inhaler for
reduced
mucous
Breaks sulfide bonds
making sputum less sticky
and easier to expectorate
Bad, sulfur odor
Albuterol
Inhaled for
(Proventil, Ventolin) Bronchiole
dilation
Sympathetic N.S.
Acts to relax muscles
around bronchioles
Throat irritation. Some risk
for tremors, restlessness
Ipratroprium
(Atrovent)
Inhaled for
Bronchiole
Dilation
Parasympathetic N.S.
Blocks acetylcholine to
reduce bronchiole swelling
Throat irritation
Constipation
Fluticasone +
Salmeterol
(Advair)
Inhaled for
Bronchiole
Dilation
Corticosteroid
Reduces inflammation
Fungal yeast infections of
the mouth
Cardiovascular Medications
Medication
Pharmacotherapeutics
Pharmacodynamics
Main Side or Adverse
Effects
Lisinopril (Zestril)
Hypertension
Protect
kidneys in
diabetes
Acts to prevent the conversion Persistent and
of Angiotensin I to
unremitting cough
Angiotensin II preventing
vasoconstriction
Losartan (Cozaar)
Hypertension
Acts directly to antagonize
Angiotensin II preventing
vasoconstriction
Rare: Edema
Clonidine (Catapres) Hypertension
Blocks Sympathetic NS:
Norepinephrine and
dopamine in the CNS
Drowsiness
Orthostatic hypotension
Metoprolol
(Lopressor)
Hypertension
Heart Failure
Arrthythmias
Beta-adrenergic Blocker:
Drowsiness
reduces affects of Symp. NS in Bradycardia
the periphery (beta receptors)
Nifedipine
(Procardia)
Hypertension
Heart Failure
Ca Channel Blocker: Slows the
influx of calcium into cells
Hypotension
Worsened ischemia
Amlodipine
(Norvasc)
Hypertension
Heart Failure
Ca Channel Blocker: Slows the
influx of calcium into cells
Hypotension
Worsened ischemia
Cardiovascular Medications
Medication
Pharmacotherapeutics
Pharmacodynamics
Main Side or Adverse
Effects
Furosemide
(Lasix)
Rapid diuresis
Acts in the loop of Henle to
prevent water and electrolyte
reabsorption
Low electrolytes
especially Potassium
Dehydration
Hydrochlorothiazide (HCTZ)
Daily Diuresis
Not PRN
Hypertension
Acts in distal tubules of
kidneys to prevent water &
electrolyte reabsorption
Low Potassium
Nitroprusside
Hypertensive
crisis
Given IV
Potent vasodilation
Must be on cardiac
monitor
Digoxin (Lanoxin)
Heart failure
Coronary
artery disease
Oral Sympathetic NS
stimulation
Bradycardia
Hold if HR<60
Dopamine
Hypotensive
Crisis
Sympathetic NS Stimulation
IV: Rapidly increases BP and
HR
Must be on cardiac
monitor
Epinephrine
Cardiogenic
shock
Sympathetic NS Stimulation of Must be on cardiac
all receptors
monitor
Vascular Medications
Medication
Pharmacotherapeutics
Pharmacodynamics
Main Side or Adverse
Effects
Atorvastatin
(Lipitor)
Lower total
cholesterol
Work in the liver to prevent
the formation of cholesterol
Muscle cramps and
breakdown
Ezetimide
(Zetia)
Lower LDL
cholesterol
Work in the gastrointestinal
system to block the
absorption of cholesterol
Diarrhea, gas, bloating
Heparin
IV or SQ
anticoagulant
Works in the clotting cascade
to prevent blood clotting
Toxicity monitored by
aPTT.
Warfarin
(Coumadin)
Oral
anticoagulant
Prevents the synthesis of
Vitamin K
Bleeding. Dose
estimated by PT, INR
Clopidogrel
(Plavix)
Oral
anticoagulant
Inhibits platelet aggregation
Bleeding
Neutropenia
Enoxaparin
(Lovenox)
IV or SQ
anticoagulant
Works in the clotting cascade
to slow blood clotting
Bleeding
Injection site bruising
Alteplase
(tPA)
Destroys
existing clots
Prevents fibrin from forming
and breaks it apart
Extreme Bleeding
Learning Activity
Due before Exam on March 30th:
• Complete Case Study: Deep Vein Thrombosis
• Post to Assignments