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Diuretics
A patient who is allergic to sulfa and need a
diuretic. Which of the following is an option in this case?
A. Indapamide
B. Ethacrynic acid
C. Chlorthalidone
D. Bumetanide
E. None of the above
Thiazide Diuretics
Thiazide diuretics
Thiazide diuretics are used in all of the following
patients EXCEPT:
A. Prevention of renal calculi
B. Hypertension
C. Edema
D. Ascites due to liver cirrhosis
E. Preeclampsia of pregnancy
F. None of the above (TD are used in all of the above
conditions)
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Thiazide diuretics
Thiazide diuretics are contraindicated in all of
the following patients EXCEPT:A. Hypersensitivity
B. Anuria
C. Diabetes incipidus
D. Hepatic coma
E. None of the above (All of above are contraindications)
Thiazide Diuretics
Thiazides diuretics cause all of the following
electrolyte abnormalities EXCEPT
A. Hypokalemia,
B. Hyponatremia
C. Hypochloremia
D. Hypomagnesemia
E. Hypocalcemia
F. None of the above (all abnormalities)
Thiazide Diuretics
Hypokalemia
• Risk with topiramate, steroids and salbutamol
• Hypokalemia the risk of digoxin toxicity ,
arrhythmia and respiratory depression when used with curari NM blockers
• Management: (more under hypokalemia)
• Monitor K+ level
• Management: K+‐rich food (prevention for K+ 3 –3.5mmol/L), K+ supplement or K+ sparing diuretic (if K+
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Thiazide Diuretics
Hypotension
–
Orthostatic: Risk by alcohol, opioids, barbiturates
– When used with other antihypertensive agents excessive hypotension
• Management: Start new agent(s) at low dose OR the dose of current agent before starting new one.
– When used with rituximab (Rituxan –antineoplastic) excessive hypotension
• Management: hold thiazide 12 hours prior to rituximab
Thiazide Diuretics
Hypercalcemia
• mobilization and excretion of calcium
• Risk by Ca+2 supplement, vit. D, and
Hyperparathyroidism
• Management:
– Monitor Ca+2
– D/C supplements if necessary
Thiazide diuretics
Thiazide diuretics would worsen all of the
following medical conditions EXCEPT:
A) Gout
B) Diabetes
C) Hyperlipidemia
D) Raynaud’s phenomena
E) None of the above (all will get worse)
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Thiazide Diuretics
• Patient on HCTZ experience reduced kidney
function with CrCl = 25ml/min, what should we do?
A. Switch to furosemide
B. Switch to metolazone
C. Switch to chlaorthalidone
D. All of the above
E. A & B only
Thiazide Diuretics
• Which of the following is NOT true about indapamide?
A. indapamide is superior to HCTZ in hyperlipidemia and diabetes
B. Indapamide + perindopril can reduce the risk of stroke
C. Common side effects with indepamaide: Headache/ dizziness
D. It is eliminated by the kidney
E. All of the above (none is true)
Thiazide Diuretics
When counseling the patients on thiazde diuretics, are the following statements true or false:
A. Take with or without food
B. Avoid sun exposure, wear protective cloths, and use sun screen
C. Avoid when breastfeeding
D. Should expect the effect in 1 – 2 hours but drop in blood pressure may take few days
E. Swallow whole, do not chew or crush
F. It can cause dry eye, be careful if you use contact lenses
G. Eat a banana every day
H. Avoid after 4:00 pm
I. Not effective if CrCl
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Loop Diuretics
Loop diuretics
Indications:
– Edema in HF, liver cirrhosis, renal disease and
nephrotic syndrome (sliding scale)
– Mild‐moderate HTN particularly in patients with
HF or CKD (not 1st line)
– Oliguria
– Treatment of hypercalcemia
Loop diuretics
Indicate if each of the following statements is true or false about loop diuretics:
A. They are potent diuretic
B. Cause hypercalcemia
C. uric acid and BG level D. Do NOT restrict salt
E. Do not use injections if it turns yellow
F. D/C IV furosemide 2 days prior to surgery
G. When switching from IV to oral, reduce the dose by 50%
H. Avoid doses after 4:00 pm to avoid night time diuresis
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Loop diuretics
Which of the following is NOT true about
furosemide solution?A) Dispense in original tight, light resistant glass
container
B) Store at controlled room temperature
C) Discard 120 days after opening the bottle
D) It contains 11% alcohol
E) None of the above (All true)
Loop diuretics
• Furosemide can cause OTOTOXICITY. Are the
following statements true or false?
– It can be permanent deafness
– Develop slowly in ≈ 6 years
– Early symptoms may be tinnitus
– Risk with aminoglycosides and cisplatin
– Risk with slow IV administration
– Risk with severe renal impairment
ACEI
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Understand RAAS
http://www.cvphysiology.com/Blood%20Pressure/BP015.htm
ACEI
Pharmacology
Inhibition of Angiotensin II formation
• Hypertension: vascular resistance systolic
and diastolic BP
• HF: cardiac output ( HR x SV = CO)
Accumulation of bradykinin (ACE is also called
bradykininase)
• Vasodilation
ACEI
Indications: Indication may very by agent. Class effect is assumed
• 1st line for HTN and HF
• Slow down nephropathy
– In diabetics +/‐ proteinuria – In non‐diabetic nephropathy
• Post MI
– mortality
– hospitalizations
– complications such as HF
Less effective in African
American unless used with
thiazide diuretics but can
be used in MI, HF and CKD
Less effective in African
American unless used with
thiazide diuretics but can
be used in MI, HF and CKD
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ACEI
Contraindications:
• Hypersensitivity (no cross sensitivity)
• History of angioedema
• Pregnancy (malformation in the 1st and
complications in the 2nd and 3rd trimesters)
• Lactation
ACEI
Adverse effects:
• Angioedema:
– 0.5%
– Risk in African American
– Management:
• Educate the patient
• Involve larynx or tongue (can be fatal) epinephrine
• Lips and face D/C therapy
ACEI
Adverse effects:
• Hypotension:
– Risk by volume depletion, HF, diuretics, hyponatrmia
and dialysis
– Management:
• If on diuretic start ACE at ½ the usual dose
• educate patient to consult physician if vomiting or diarrhea
develop or fluid intake
• When initiating ACEI therapy: monitor BP x 2 hours post first
dose
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ACEI
Adverse effects:
• Rash
– More with captoptil (contains sulfa)
– Onset is ≈ 1 month. May spontaneously disappear
– Management: AH, or D/C ACEI
• Hepatotoxicity: transaminases, bilirubin, jaundice
• Reversible loss of taste = dysguesia (which agent?)
• Photosensitivity (which agent?)
• Blood dyscrasias
• Pancreatitis
ACEI
Drug interactions:
– Iron dextran (IV) ACEI IV iron side effects
particularly anaphylactic reaction.
– Allopurinol ACEI risk of hypersensitivity and
SJS.
• If combination is required monitor for
hypersensitivity for a minimum of 5 weeks.
– Drugs that K+ level monitor K+ level
– ACEI Li+ level ( renal clearance) monitor Li+
ACEI
Drug interactions:
• Combination causing hypotension:
– 1 blockers Excessive hypotension
• Management: start therapy at low dose and monitor BP
– Thiazide diuretics Excessive hypotension
• Management:
– if possible D/C thiazide diuretic 1 week before starting ACEI. If not, then..
– Start ACE I at low dose
– Patient to remain supine for ≥ 3 hours after first ACE dose
– Consider increasing Na+ intake
– Monitor BP when initiating ACEI therapy
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ACEI
Monitoring
• K+ level and SCr at baseline and 1 – 2 weeks after initiation of therapy or dose increase
then annually
– If SCr > 30% of the baseline may D/C ACEI
– K+ > 5.6mEq/ml may D/C ACEI
Same monitoring for ARBSame monitoring for ARB
ACEI
NOTES on ACEI
• Which ACE is available for IV administration?
• Which ACEI are approved in HTN in children?
• Which ACEI do not require dose adjustment in
patients with renal failure?
• Which ACEI do not have active metabolites?
ACEI
NOTES on ACEI
• Which ACEI are NOT prodrugs? __________________
• The absorption of which ACEI are not affected by food?
_______________________________(other affected,
consequence unclear)
• When switching from IV enalapril to po start with ________
• All once daily (EXCEPT_______________________)
• Captopril take _____________meals
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ACEI
NOTES on ACEI
• Usual daily doses captopril 50 – 150mg, enalapril 10 – 40mg
• Captorpril has short duration can be used
for management of acute HTN
• Perindopril + indapamide decrease stroke
ACEI
A patient who takes ramipril should contact his physician if he experiences all of the following adverse reaction EXCEPT:
A. muscle weakness and slow or irregular heart rate
B. Swelling of the face, lips tongue or throat
C. Dry hacking and persistent cough
D. Reduced urine output
E. All of the above
ACEI
Counseling for ACEI:
• Take with or without food (except captopril 1h before meals)
•
Can crush
or chew
tablets
(Ramipril capsules
can
be
opened)
• Take at the same time every day
• Continue taking the medication even if you do not feel any better
• Avoid eating too much food rich in potassium
• It may cause dizziness, change your position slowly
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ARB
ARB
Mechanism:
• Block angiotensin II type 1 receptors (AT1)
Indications:
• 1st line agent in patients uncomplicated HTN and
HTN + diabetes, ISH and LVH
• In HF: as alternative to or in combination with to
ACEI
• All other indications: alternative to ACEI
ARB
Switching patients from ACEI to ARB is a choice in patients who take ACEI and develop:
A) Hyperkalemia
B) CoughC) Angioedema
D) Renal failure
E) A & B
F) B & C
G) B & D
H) All of the above
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ARB
Combining an ACEI and ARB can cause all of the
following EXCEPT: A) BP
B) Worsen RF,
C) risk syncope,
D) Worsen HF
E) risk of stroke
F) risk of hyperkalemia
Direct Renin Inhibitor
Direct Renin Inhibitor
Aliskiren
• Indications: HTN +/‐ diuretics and DHPCCB
•
CI:
hypersensitivity, pregnancy,
Hx of
angioedema, combination with ACEI/ARB
• ADR: K+, angioedema, cough (rare),
headache, diarrhea, rash, gout
• DI: Avoid use with cyclosporine and azoles.
Grapefruit juice,
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Beta Blockers
Beta blockers ‐ Effect
Which of the following is NOT an effect of beta
blockers on the cardiovascular system?
A. Decrease heart rate
B. Decrease cardiac output
C. Decrease cardiac contractility
D. Improve coronary blood supply
E. None of the above (all of the above are
effects)
Beta blockers – Indications
All of the following are indications of beta blockers EXCEPT
A. HTN
B. AnginaC. Post MI
D. Migraine
E. Heart failure
F. Arrhythmia
G. None of the above (All above are indications)
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Beta blockers ‐ Contraindications
Which of the following is NOT a contraindication for beta blockers?
A. Asthma and COPD
B. Bradycardia
C. AV block
D. Overt heart failure
E. Tremors
F. Raynaud's disease
G. None of the above (all of the above are contraindications)
Beta blockers – Indications
Specific indications per agents
Propranolol
Tremors,
Also used for: bleeding esophageal varices,
thyrotoxicosis, anxiety
Sotalol ONLY indicated for arrhythmia
Carvedilol ONLY indicated for stable HF
Propranolo &
Timolol Headache (others can also be used)
Beta blockers – Classifications
All of the following beta blockers have intrinsic
sympathomimetic effect EXCEPT:
A. Pindolol
B. Metoprolol
C. Acebutolol
D. Oxprenolol
E. None of the above (All have ISA)
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Beta blockers – Classifications
All of the following beta blockers are cardio
selective ExceptA. Bisoprolol
B. Pindolol
C. Metoprolol
D. Acebutolol
E. Atenolol
F. None of the above (All are selective)
Beta blockers – Classifications
Which of the following beta blockers block both
beta and alpha receptors?
A. Pindolol
B. Carvedilol
C. Sotalol
D. Timolol
E. Labetalol
Beta blockers
When beta blockers is needed for a patient with
high risk of stroke, which beta blocker should be
used?
A. A non selective beta blocker
B. A beta blocker with high CNS penetration
C. A cardio‐selective beta blocker
D. A beta blocker with ISA
E. Any of the above
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Beta blockers
Beta blockers would worsen all of the following medical conditions EXCEPT
A. Depression
B. Hyperlipidemia
C. Hyperthyroidism
D. Diabetes
E. Psoriasis
F. Erectile dysfunction
G. Patients with anaphylactic reaction who need epinephrine
H. None of the above (all of the above may get worse)
Beta blockers
All of the following patients will benefit from a beta blocker with ISA EXCEPT:
A. A patient with excessive bradycardia when using other beta blockers
B. Patient post MI
C. A patient with Diabetes
D. Patients with cold extremities
E. A patient with hyperlipidemia
F. A patient with asthma symptoms
Beta blockers
Which of the following beta blockers has an
active metabolite?
A. Atenolol
B. Metoprolol
C. Propranolol
D. Sotalol
E. Labetalol
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Beta blockers – Adverse Reactions
• CNS: depression, dizziness, fatigue, weakness, vivid dreams, confusion, impaired concentration/ memory,
hallucination, insomnia, somnolence (propranolol has
most CNS effects)
• CVS: hypotension, Orthostatic hypotension (more with Carvedilol), bradycardia, cold extremities
• Respiratory: dyspnea, bronchospasm, wheezing,
• GIT: N/V, constipation, diarrhea, dry mouth
• Dermatology: rash, exacerbate psoriasis, photosensitivity
• Sexual dysfunction
Beta blockers
NOTES:
• Beta blockers may be ineffective in preventing
cardiovascular events in people who smoke.
• Avoid abrupt withdrawal severe HTN and
risk of angina. Taper over 2 – 4 weeks period
Beta blockers – Interactions
• CYP2D6 inhibitors increase levels of
propranolol and metoprolol and carvedilol
• Digoxin, amiodarone, diltiazem, verapamil: ↑
bradycardia, additive cardiodepressant effect
• How to manage the bradycardia caused by
Beta blockers? Atropine
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CCB
CCB can be used for all of the following indications EXCEPT:
A) HTN
B) Migraine
C) subarachnoid hemorrhage
D) A. Fib & A. flutter
E) Prinzmetal angina
F) Stable angina
G) None of the above (All are indications)
CCB
Which of the following is NOT a contraindication to CCB?
A. Hypersensitivity
B. Patient at risk of severe hypotension
C. Severe bradycardia
D. Recent IM
E. Severe heart failure
F. Patient with AV block
G. Concomitant use with cardiac depressant drugs
H. None of the
above
(all
are
contraindications)
CCB
Which of the following CCB does NOT interact with grapefruit juice?
A. Amlodipine
B. Nifedipine
C. Felodipine
D. Diltiazem
E. Verapamil
F. None (all interact)
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Nitrates
Nitrates
Mechanism:
• All prodrugs liberate nitric oxide
(endothelium derived relaxing factor)
vasodilatation
– Coronary artery Cardiac O2 delivery
– Veins preload O2 consumption
• It also has smooth muscle relaxing effect
Nitrates
Pharmacokinetics:
• Absorption through GIT and skin
•
Tolerance develop
particularly
with
long
t ½
preparations keep 10‐12 hours drug free
interval ( exercise tolerance and frequency
and severity of angina at the end of dose
interval) keep drug free period at night
(less likely to experience angina)
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Nitrates
Which if the following is NOT a contraindication
for nitrates?A) Severe anemia
B) Hypotension
C) Cranial hemorrhage
D) Uncontrolled hypovolemia
E) None of the above (all are contraindications)
Nitrates
Adverse reactions:
• The most frequent is headache (50%), in
few days (may take acetaminophen)
• Dizziness, hypotension, flushing, reflex
tachycardia, rash, nausea, vomiting,
dermatitis (with topical), muscle twitching,
blurry vision.
Nitrates
Drug interactions:
• Excessive hypotension with alcohol,
antihypertensive drugs and PDE‐5 inhibitors
• Drugs that may precipitate angina ex. Ergot
• IV nitroglycerin heparin resistance
• When PDE‐5 inhibitor is given with nitrate
separate by at least 24 hours (safety not
established)
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Nitrates
Which of the following is TRUE about using sublingual NTG ?
A. Patient should be instructed to sit down before using NTG
B. Acetaminophen can be used to treat headache
C. Store at room temperature.
D. SL NTG can be used 5‐10 minutes before angina‐provoking activities
E. SL NTG has a 1 – 5 minutes onset
F. All of the above are true
Nitrates
Which of the following is true about taking SL NTG in patients who experience chest pain?
A. Call 911 then use 1 spray every 5 minutes x 3
B. Use 1 spray SL and then call 911 and repeat the dose every 5 minutes x 3 if needed
C. Use 1 spray SL, wait for 5 minutes, call 911 if pain persists and repeat x 2 every 5 minutes if needed
D. Use 1 spray SL every 5 minutes x 3 doses and call 911 right after the 3rd dose (do not wait 5
minutes)
Nitrates
Which of the following is NOT true about using sublingual NTG TABLETS:
A. If tablets sting when placed SL, this means they are no longer potent discard
B. It is recommended to renew the stock every 6 monthsC. Once opened, remove the cotton plug permanently
D. Tablet can be placed under the tongue or in buccal pouch
E. NITROSTAT may cause a false test result of decreased serum cholesterol.
F. Do not chew, crush, or swallow NITROSTAT tablets.
G. None of the above (all of above are true)
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Nitrates
Which of the following is NOT true about using sublingual NTG
SPRAY:
A. It should not be inhaled
B. Patient must close mouth immediately after use
C. It can sprayed on the tongue
D. The drug maintain its potency till the expiry date on canister
E. Do NOT shake
F. Prime, re‐prime if not used for two weeks
G. None of the above (all true)
Nitrates
Which of the following is NOT true about NTG patch?A. The blood level becomes unpredictable 2 hours after
removing the patch
B . One patch can keep steady state for 24 hours
C. Patch must be removed before cardioversion
D. Avoid extremities below the knee or elbow
E. Avoid skin folds, scar tissue, burned or irritated areas.
F. Wash skin area with soap and water
G. Use a different application site every day.
H. Skin may feel warm and appear red and will disappear
I. If the area feels dry, you may apply a soothing lotion.
J . All of the above
Nitrates
Which of the following is NOT true about using NTG ointment?
A. Applied in the morning and then again 6 hours later
B. Wipe off the ointment at bedtime
C. Dose is measured in grams of ointment D. Dose must be applied to an area of minimum of 5 x 7.5cm
E . D o not rub into the skin
F. Applicator can be taped in place to cover the ointment
G. It can stain clothing so completely cover the dose measuring applicator with a plastic kitchen wrap
H. The dose : area ratio must be kept constant
I . Al l of the above are true
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Digoxin
Digoxin
Indications:
– HF (add on therapy, hospitalization and improve
symptoms exercise tolerance, no effect on
mortality)
– A.Fib (control ventricular rate)
Contraindications:
– Ventricular tachycardia
– Hypersensitivity reaction
Digoxin
Which of the following is NOT true about the
effect of digoxin on the heart?
A. HR
B. contractility
C. LVEF
D. Cardiac output
E. None of the above (all correct)
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Digoxin
The dose of digoxin depends on all of the
following EXCEPT: A. Age
B. Renal function
C. Lean body weight
D. Concomitant disease states
E. Liver function
F. None of the above (All are important)
Digoxin
What is the objective of digitalization?
A. To build body stores of 4 to 6 µg/kg
B. To build body stores of 8 to 12 µg/kg
C. To build body stores of 16 to 24 µg/kg
D. To build body stores of 24 to 36 µg/kg
E. None of the above
Digoxin
Digitalization: two approaches:
• Gradual digitalization: Give maintenance dose to allow slow accumulation (will take about 5 half ‐
lives ≈ 1 to 3 weeks) • Rapid Digitalization: Give a single initial dose of
500 to 750 µg (0.5 to 0.75 mg) followed by 125 to 375 µg (0.125 to 0.375 mg) doses given at 6‐ to 8‐hour intervals until clinical evidence of an adequate effect is noted (monitor after each dose)
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Digoxin
Drugs Effect
Cholestyramine, antacid, adsorbent
antidirrhea, sulfasalazine, sucralfate,
metocloperamide, St. John’s wort
Digoxin level (take 8 hours before
cholestyramine and adsorbent and 2
hours apart of antacids)
Omeprazole, cyclosporine, flecainide,
itraconazole, quinidine,
spironolactone, quinidine, NSAIDs
(particularly indomethacin)
Digoxin level (different mechanisms)
monitor digoxin level
Beta blockers, verapamil, diltiazem,
nifedipine,
Further depression of HR monitor
digoxin level and HR
Antibiotics Digoxin inactivation effect
Thiazide and loop diuretics K+ toxicity (monitor digoxin level)
Sympathomimetic agents Risk of arrhythmia
Thyroid hormone Response to digoxin
Digoxin
All of the following symptoms does NOT suggest
digoxin toxicity?
A. Anorexia
B. Nausea
C. Vomiting
D. Fluid retention
E. Arrhythmia
Digoxin
Adverse reaction:
nausea, vomiting, headache, diarrhea, mental
disturbances , dizziness
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Digoxin
Which of the following is NOT true concerning
digoxin toxicity?A. Therapeutic digoxin level is 0.8 to 2.0 ng/mL
B. Hypokalemia risk of digoxin toxicity
C. Digoxin toxicity may develop even when the
serum concentration is therapeutic
D. Hypercalcemia risk of digoxin toxicity
E. None of the above (ALL true)
Digoxin
Which of the following is NOT true about treating bradycardia in patients with digitalis toxicity?
A. Treat bradycardia even if asymptomatic
B. Digoxin immune fab should be used to reverse digoxin toxicity
C. Atropine can be used to reverse bradycardia
D. Temporary cardiac pacemaker may be required
E. None of the above (all true)
Digoxin
Monitoring:
• Digoxin serum level
• BUN and SCr
• Electrolytes
• Weigh patient daily.
• Measure and monitor urine output daily
• Monitor pulse daily.
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Miscellaneous Agents
Vasodilators
Which of the following agents is direct acting
vasodilator?
A) Methyldopa
B) Hydralazine
C) Guanethidine
D) Clonidine
E) All of the above
Vasodilators
Notes:
• Vasodilation compensatory stimulation of SNS Reflex tachycardia, renin release (Na/H2O
retention), in cardiac output and HR – effect
– Can precipitate angina
• Uses:
• 3rd line agent agents in HTN
• Hydralazine + nitrates in HF
• In severe chronic kidney disease and in kidney failure.
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Vasodilators
How to prevent the compensatory mechanism and angina precipitation in patients who receive vasodilators?
A) Brief drug holidays should be scheduled to interrupt the compensatory mechanism
B) Patients should be stabilized on ACE or ARB before starting hydralazine therapy
C) Patients should be stabilized on beta blockers + thiazide diuretics before starting vasodilators
D) Patient should advised to avoid sudden changes in position in the first two weeks of therapy
Vasodilators
Hydralazine:
• Used in combination with Nitrates in HF
mortality, hospitalization, QOL (particularly
in African American).
• The combination ADR (hypotension,
headache, flushing, dizziness, GI distress)
Vasodilators
Hydralazine:
• Adverse Reactions:
– Reversible, dose‐dependent lupus‐like syndrome
(keep daily dose
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Vasodilators
Minoxidil:
• More potent vasodilator dramatic compensatory especially Na/H2O retention
precipitate HF
• ADR:
– Hypertrichosis (reversible, involve face, arms,
back, and chest)
Vasodilators
Minoxidil should be reserved for:
A) Patients with HTN and alopecia
B) Patients with HTN who cannot tolerate ACEI
C) Patients with difficult to control hypertension
D) Patients who experience lupus‐like symptoms
while on hydralazine
α1‐Receptor Blockers
Mechanism: Blocking α1‐receptor
vasodilatation
– Do NOT CVA so not used as 1st line therapy
– Useful in males with HTN and BPH (but must be
used in combination with other agents)
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Central α2‐Agonists
Clonidine
•Can be used for acute increase in BP (0.1mg x 1 then 0.1mg q1h prn)
•Avoid in diabetes (autonomic neuropathy)
Blood Coagulation
Source: http://almostadoctor.co.uk
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Platelet aggregation inhibitors
Platelet aggregation inhibitors
Three classes:
• ASA
• Dipyridamole
• ADP receptor blockers:
– Clopidogrel
– Prasugrel (Effient)
– Ticagrelor (Brilinta)
– Ticlopidine (Ticlid)
ASA
Indications & doses
• Acute MI ( mortality) – Chew/crush 160‐162mg ASAP then same dose qd x30 days then reassess
•
1ry and 2ry prevention of MI and stroke in
patients at risk 80‐325mg po daily
• Unstable angina ( mortality)
• risk of TIA 80‐325mg po daily
• Prevention of VTE after total hip replacement ‐650mg po BID 1 day before surgery and continue for 14 days
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ASA
Mechanism
Inhibits COX1
inhibits
TXA2
synthesis
irreversible inhibition of platelet aggregation
Contraindications: – Hypersensitive
– History of salicylates/NSAID ‐induced asthma
– Patients on MTX dose ≥ 15 mg/week
– 3rd trimester of pregnancy
– Active bleeding
– Reye’s syndrome
– Severe renal and hepatic impairment
ASA
Drug Interactions
• Drugs inhibiting clot formation: effect and risk of bleeding
• Glucocorticoids /SSRI: risk of bleeding
• NSAIDS risk of ulcers and GI bleed
• Ibuprofen platelet aggregation inhibition by ASA
• ASA effect of hypoglycemic agent (dose‐dependent)
• ASA level of valproic acid and digoxin
• ASA effect of uricosuric agents (at large dose) and antihypertensive drugs (dose‐dependent)
ASA
Adverse effect (mostly dose‐related) • GI: upset (5%) bleed (2.7%)
• Tinnitus, vertigo, hearing loss
• Rash, fatigue, muscle weakness, gout, leukocyte/platelets
Notes: • ASA should be discontinued 7 – 10 days prior to
surgery (except CABG or moderate to high CV risk)
• Fresh platelets are used as antidote for ASA
• 5 – 10 % may develop platelet resistance
• Take with food
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ADP receptor blockers
GH will start clopidogrel following stent
placement. GH is currently taking PPI for prevention of GI bleed. Which of the following PPI will least likely interact with clopidogre?
A) Omeprazole
B) Lansoprazole
C) Pantoprazole
D) Rabeprazole
E) All are equal
ADP receptor blockers
What advantage does clopidogrel offer over ASA
A) Lower cost
B) More effective
C) Less ADR
D) Longer duration
E) Higher potency
F) All of the above
ADP receptor blockers Cl op id og rel Pra su gre l T ica grel or T ic lo pi di ne
Interaction
PPI (EXCEPT
pantoprazole)
activation &
effect
Azoles antifungal
activation & effect
Nothing
significant
3A4 inhibitors
(azoles, macrolides,
diltiazem, PI)
effect (CI)3A4 inducers
(rifampin,
phenytoin,
carbamazepine)
effect
Ticagrerol
simvastatin/
digoxin level
(monitor digoxin)
phenytoin,
and
theophylline
level
cyclosporine
levelAntacids
ticlopidine
level
All interact with drugs affecting blood clot formation
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UFH and LMWH
UFH and LMWH
Mechanism:
Bind to and enhance the effect of Antithrombin
ACCELERATE the inactivate active coagulation
factors (Mainly thrombin (IIa) and factor Xa)
slow down the coagulation process without
breaking down (lysis) the existing clot (i.e. not
thrombolytic)
UF LMWH
Large molecule Smaller (enz. degradation of UH)
Accelerate inactivation of factors
IIa (thrombin) and factor Xa
Accelerate inactivation of factor Xa
2 – 4 times > factor IIa
Highly bound to plasma protein Insignificant binding
Removed by endothelial system (saturable) at low dose and renally
(non saturable) at high dose
Removed renally (non saturable) only. Elimination is NOT dose‐
dependent
T½ of 0.5 – 2 h (Dose‐dependent) T½ of 2 – 4 h (Not dose dependent)
Variable SC bioavailability: 10 –
30% (low dose) and > 90% (high
dose)
Consistent bioavailability (>90%)
Unpredictable dose‐response
(MONITOR using aPTT)
Predictable dose‐response (No
need to monitor)
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UFH and LMWH
Indications
• UH and LMWH – Treatment of DVT
– Prevention (ex. Following orthopedic and high risk abdominal surgery)
• Heparin: – Prevent clotting during dialysis
– Maintain IV line open (used as a flush)
• LMWH: – Treatment of unstable angina and ST‐segment
elevation MI
UFH and LMWH
Contraindications
• Hypersensitivity
• Confirmed Type‐II HIT
• Active bleeding (ex. ulcer, hemorrhagic stroke)
• risk of bleeding:
– Patients with clotting disorders such as hemophilia
– Severe liver damage
– Patients who had a recent surgery
– Severe hypertension
UFH and LMWH
Which of the following is an NOT an adverse
reaction of Heparin/LMWH?
A. Allergic reaction (chills, fever, rash)
B. Hematoma at injection site
C. HIT
D. Hypokalemia
E. Osteoporosis
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UFH and LMWH
Which of the following is NOT true about Type‐II
HIT?A. Immune‐mediated
B. platelet count drops below 100x109/L
C. Onset is 2 – 5 days of initiating heparin therapy
D. Complications include the formation of white
thrombosis
E. Require discontinuation of therapy
UFH and LMWH
Which of the is NOT true about treatment of
Type‐II HIT?
A. D/C heparin therapy
B. Fresh platelet transfusion to platelet count >
100x109/L
C. Platelet count will start to rise within 3 – 5 days
D. Risk of thrombosis remains high for 30 days
E. Danaparoid, lepirudin, and argatroban can be
used as alternatives.
UFH and LMWH
Drug interactions:
• Drugs affecting blood clot (oral anticoagulant,
ASA, thrombolytic agents) monitor for
increased risk of bleeding
• Heparin:
– IV nitroglycerin heparin effect (monitor)
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UFH and LMWH
Monitoring
Heparin: ‐ Platelet: q2‐3 days,
‐ aPTT : 6 hours after initiating therapy (4 h in children) x 4 then daily (monitor q4h after dose change)
‐ Anti Xa level can be also monitored
LMWH: ‐ Monitoring generally not recommended (but follow
the heparin monitoring above)
‐ Anti‐factos Xa level can be used in some cases (pregnant, obese, under weight)
UFH and LMWH
Notes:
• Pregnancy and breastfeeding
– Heparin:
• Safe in pregnancy and breastfeeding
• Altered pharmacokinetics monitor
• risk of bleeding in last trimester and postpartum period monitor
– LMWH:
• 1st choice (as per TC)
• Safe in breastfeeding
UFH and LMWH
Overdose Heparin:
• Elevated aPTT but NO bleeding: – Hold heparin, monitor patient, may restart therapy as needed
•
Bleeding (especially
aPTT >
3x
control)
– Protamine sulfate
• Complete reversal, dose required to neutralize 1000 units varies (see label)
• Do NOT exceed 20mg/min (or 50mg in 10 minutes) severe hypotension and anaphylactic reaction
– Fresh frozen plasma can be used
LMWH: – Follow same protocol
– Protamine incomplete reversal ( does not reverse Anti IIa effect)
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HIT
• Type 1 (non‐immune mediated – direct effect) – Common, mild in platelet count (remain >
100x109/L) in the first few days
– No thrombosis, may continue heparin therapy
UFH and LMWH
Which of the following is NOT true concerning
the SC self ‐administration of LMWH?
A. Should be injected in U –shaped area
surrounding navel
B. Injection site should vary daily
C. Needle must be inserted at 45 – 90 degree angle
D. The patient must sit or lye down during injection
E. None of the above (all true)
UFH and LMWH
NOTES:
• LMWH
• SC is the preferred route of administration
• Avoid in ischemic stroke until hemorrhage is ruled out• Multi‐dose vials of tinzaparin contain sodium
metabisulfite can cause anaphylactic reaction in certain people (ex. Asthmatic)
• Multi‐dose vials of all LMWH (EXCEPT Nadroparin) contain benzyl alcohol fetal toxic syndrome (avoid in pregnancy)
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UFH and LMWH
NOTES:
•
Heparin• Used IV (immediate onset) and deep SC (
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Warfarin
Mechanism:
Inhibit vitamin K‐dependent clotting factor by inhibiting vit. K epoxide reductase (VKOR) 30
– 50% reduction in factors II, VII, IX and X)
• Onset: 24 hours with peak anticoagulation in 3 – 4 days
• Duration of single dose is 2 – 5 days
• Metabolism: Multiple CYP‐450 enzymes but 2C9 is the main one.
Warfarin
Which of the following is NOT an indication for
warfarin?
A) To prevent the formation of DVT and PE
B) To prevent the extension of venous thrombosis
C) To reverse ischemia in patients with acute stroke
D) In patients with A.fib to prevent stroke
E) None (All of the above are indications)
Warfarin
Contraindications:
• Pregnancy
• Active/ uncontrolled bleeding
• Hx of warfarin‐induced skin necrosis
• Hemorrhagic tendency
• Recent or contemplated CNS or eye surgery
• Surgery involving large open space
Caution in patients with HIT (reported limb necrosis)
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Warfarin
Monitoring:
• When do we need to monitor INR?
in the following situations:
– Initiation of warfarin therapy
– Increasing warfarin dose
– Starting a new interacting drug
Warfarin
Monitoring:
• New patient:
– Week‐1: Day 3 and 5
– Week‐2: check INR twice
– Starting week‐3: weekly till INR within range x 2 weeks then every 2 weeks till within range x 1 month then monthly till stable x 3 months then every 12 weeks
• Warfarin: weekly till stable then as above
• New interacting drug: INR in 5 days then weekly as above
Monitor PT daily until INR is
stabilized in range
Monitor PT daily until INR is
stabilized in range
Warfarin
All of the following factors would affect INR
EXCEPT:
A. Comorbidities
B. Genetics
C. Diet.
D. Social history
E. Environment
F. All of the above
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Warfarin
VB calls the pharmacy today in panic. He indicates that he made a mistake and has been double the
warfarin dose by accident. What is the best response?
A. Hold warfarin and contact physician for dose adjustment
B. Contact the physician ASAP to get the INR checked
C. May intake of green leafy vegetable to decrease the effect of high dose
D. Inquire about symptoms of bleeding and advise the patient to see the physician for INR
Warfarin
VB denies any signs or symptoms suggesting
bleeding. In the absence of significant bleeding,
when should you vitamin K?
A. When INR is > 3 and 4.5 and 10
D. Vitamin K is reserved for patients with serious
bleeding only
Warfarin
If VP has serious bleeding, which of the
following is NOT true?
A. Vitamin K should be given once INR > 6
B. Should get 5‐10mg of IV vit. K
C. VP must hold warfarin
D. Factor IV prothrombin concentrate is required
E. None of the above (all true)
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Warfarin
VP is going for a minor dental surgery and the dentist and physician agreed to continue warfarin
therapy. Which of the following can be used to reduce bleeding?
A. Vitamin K 2.5 mg po 1 – 2 hours before surgery
B. Vitamin K 2.5mg IV 30 minutes before surgery
C. Tranexamic acid mouth wash pre surgery
D. Reduce warfarin dose by 15% 3 – 5 days before surgery
E. Minor dental surgeries are safe to have while on warfarin
Warfarin
Which of the following antidotes can be used to
reverse the effect of warfarin in patients with
bleeding?
A. Factor IV prothrombin complex
B. Fresh frozen plasma
C. Recombinant factor VIIa
D. Vitamin K
E. All of the above
Warfarin
Serious adverse reactions:
• Bleeding: ≈ 10% (serious ≈ 1%)
• What factors the risk of bleeding? – INR > 4 or highly variable INR
– Age > 65 – Uncontrolled hypertension
– Hx of GI bleeding
– Long duration of therapy
– Cancer
– Interacting drugs
– Liver diseases
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Spironolactone
• Mechanism: Aldosterone receptor blocker
• Indications: 1ry Hyperaldosteronism, CHF,
edema/ascites in liver cirrhosis , HTN (mild
effect, used with other agents) Hypokalemia
(treatment and prevention)
• CI: hypersensitivity, anuria, hyperkalemia (do not
start if K+ > 5mmol/L), renal impairment (do not start
in CrCl 5
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Eplerenone
Which of the following is NOT true about
eplerenone? A) It is more potent
B) Indicated only for HF and post MI
C) It cause less gynecomastia
D) It causes less impotence
E) None of the above (all true)