cvs drugs for participants 3 slides per page

8/15/2019 CVS Drugs for Participants 3 SLIDES PER PAGE

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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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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)


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


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



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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)

cvs drugs for participants 3 slides per page

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