Lecture 9+10

Question 1

ARB examples

Answer 1

Losartan / Valsartan

Question 2

ARB drug MOA

Answer 2

first-line agents
alternative for those that cant have ACEI’s

Block angiotensin-2 type 1 receptors:

decrease BP by causing arteriolar & venous dilation

Block aldosterone secretion → decrease Na+ & H20
retention

decrease diabetic nephropathy

DOES NOT increase bradykinin

Question 3

AE’a of the ARB’s

Answer 3

Similar to those of ACE inhibitors

Dry cough does not occur

Angioedema risk is significantly lower than with
ACEI’s

Losartan reduces plasma uric acid levels by inhibiting
URAT1 transporter

Question 4

ARB contraindication

Answer 4

Pregnancy

Patients with bilateral renal artery stenosis

Question 5

renin inhibitor example

Answer 5

Aliskiren

Question 6

MOA of renin inhibtors

Answer 6

Inhibits enzyme activity of renin and prevents conversion of angiotensinogen into angiotensin I

Inhibits production of both angiotensin II and
aldosterone

Question 7

AE of renin inhibitors

Answer 7

• Similar to those of ACE inhibitors
• Dry cough does not occur (due to no effect on
bradykinin levels)
• Angioedema risk is significantly lower than with
ACEI’s

Question 8

examples of Ca channel blockers

Answer 8

first line for black/elderly patients

non-dihydropyridines:
Verapamil / Diltiazem

Dihydropyridines:
Nifedipine / Amlodipine

Question 9

verapamil

Answer 9

non-dihydropyridine

Significant effects in cardiac & vascular smooth muscle

Used to treat angina, supraventricular tachyarrhythmias, hypertension, migraine & cerebral vasospasm

Question 10

Diltiazem

Answer 10

non-dihydropyridine

Effects in both cardiac & vascular smooth muscle

Used to treat angina, hypertension, supraventricular
tachyarrhythmias & cerebral vasospasm

good side-effect profile

Question 11

Amlodipine and nifedipine

Answer 11

dihydropyridines

Greater affinity for vascular Ca2+-channels than for cardiac Ca2+-channels

Reduce Ca2+ entry into smooth muscles to cause
coronary & peripheral vasodilatation & lower BP

Primarily used in treating hypertension

Question 12

MOA of Ca blockers

Answer 12

If you block the Ca channel… there is less movement of Ca, and thus decreased force of muscle contraction

Question 13

clinical apps. of Ca blockers

Answer 13

• Hypertension (1st line, particularly for black and/or
elderly patients)
• Have intrinsic natriuretic effect (no need for diuretic)

Question 14

risk of taking Ca channel blockers

Answer 14

increased risk of MI ((excessive vasodilation & reflex cardiac stimulation)

High-doses of short-acting dihydropyridine

Question 15

AE of verapamil

Answer 15

Constipation (~7%), negative inotropic effects, gingival

hyperplasia

Question 16

AE of Diltiazem

Answer 16

Negative inotropic effects

Question 17

AE of the dihydropyridine’s

Answer 17

Hypotension, peripheral edema (esp. feet & ankles),
dizziness, headache, fatigue, gingival hyperplasia,
flushing, reflex tachycardia can occur (especially in
short-acting preparations)

Question 18

contraindications of the dihydropyridine’s

Answer 18

in patients taking b-blockers, or who have 2nd or 3rd degree AV block, or severe left ventricular systolic dysfunction

Question 19

use thiazides 1st line for?

Answer 19

first line treatment for most, especially AA and elderly.

Question 20

when to use loop diuretics

Answer 20

Used primarily in patients who do not respond to

thiazide therapy adequately

Question 21

beta blockers

Answer 21

Propranolol / Metoprolol / Atenolol / Pindolol

Used only as add-on therapy to first line agents in
primary prevention patients

First-line therapy only for patients with coronary
artery disease, heart failure or post-MI

Question 22

MOA of the Beta blockers

Answer 22

Reduce BP by cardiac output, contractility & heart rate

Inhibit both release of norepinephrine and renin (b1 R) (→ decrease in angiotensin II & aldosterone secretion)

takes weeks to develop full effects

Question 23

AE of beta blockers

Answer 23

hypoglycemia 
bradycardia 
hypotension 
decreased libido 
disrupted lipid metabolism 

no one can take if they have pulmonary issue

Question 24

alpha blocker examples

Answer 24

Prazosin / Doxazosin

Question 25

MOA of alpha blockers

Answer 25

Competitively block a1 -adrenoceptors decreased peripheral vascular resistance & arterial BP by relaxing both arterial & venous smooth muscle no long term tachy can have H20 and Na retention can lower BP.. but have more AE

Question 26

clinical app of alpha blockers

Answer 26

hypertension benign prostatic hyperplasia Have been used in heart failure

Question 27

AE of alpha blockers

Answer 27

orthostatic hypotension Dizziness, drowsiness, headache, lack of energy, nausea, and palpitations, Doxazosin shown to increase rate of congestive HF

Question 28

mixed alpha and beta blocker | used? adverse?

Answer 28

labetalol Used in hypertension management (safe in pregnancy) IV labetalol = rapid reduction in BP no reflex increase in HR or cardiac output AE: orthostatic hypotension

Question 29

central alpha2 agonist

Answer 29

clonidine reduces sympathetic outflow decrease in PVR and CO = lower BP does not decrease renal blood flow used in HTN management or crisis

Question 30

clonidine AE

Answer 30

Drowsiness, dry mouth, dizziness, headache & sexual dysfunction occur commonly Rebound hypertension may occur following abrupt withdrawal

Question 31

methyldopa

Answer 31

central alpha2 agonist decrease peripheral resistance and BP does not decrease renal blood flow or CO used for pregnancy induced HTN or HTN management

Question 32

AE of methyldopa

Answer 32

Sedation, drowsiness, dizziness, nausea, headache, weakness, fatigue, sexual dysfunction, hypoprolactinemia Nightmares, mental depression, vertigo (infrequent) can develop of + coomb's test (long term)

Question 33

direct vasodilators

Answer 33

Hydralazine / Minoxidil not first line for HTN direct acting on SM Produce reflex tachycardia, increase plasma renin → Na+ & H20 retention Major side effects can be blocked if combined with diuretic & b-blocker

Question 34

hydralazine

Answer 34

direct vasodilator acts mainly on the arterioles Used to treat pregnancy induced hypertension / preeclampsia Used in management of hypertension as last-line therapy

Question 35

AE of hydralazine

Answer 35

Fluid retention & reflex tachycardia are common Reversible lupus-like syndrome Headache, nausea, sweating, flushing Usually administered with b-blocker & thiazide

Question 36

minoxidil

Answer 36

direct acting vasodilator Causes direct peripheral vasodilatation of arterioles Oral treatment for severe-malignant hypertension (refractory to other treatments)

Question 37

AE of minoxidil

Answer 37

Reflex tachycardia & fluid retention may be severe (combine with loop diuretic & b-blocker) ``` Causes hypertrichosis (also used topically to treat male pattern baldness) ```

Question 38

pulmonary HTN

Answer 38

An increase in blood pressure in the pulmonary artery, pulmonary vein or pulmonary capillaries ``` Treatments • Prostaglandins (epoprostenol) • Inhibitors of endothelin synthesis and action (bosentan) • Vasodilators (sildenafil) ```

Question 39

Epoprostenol

Answer 39

synthetic PGI Lowers peripheral, pulmonary, and coronary resistance Adverse effects include flushing, headache, jaw pain, diarrhea and arthralgias

Question 40

Bosentan

Answer 40

Nonselective endothelin receptor blocker Blocks both the initial transient depressor (ETA) and the prolonged pressor (ETB) responses to endothelin Pregnancy category X

Question 41

Sildenafil (vasodilator)

Answer 41

Inhibitor of phosphodiesterase 5 (PDE5) Increased cGMP → smooth muscle relaxation Adverse Effects: headache, flushing, dyspepsia, cyanopsia Contraindications: Nitrates

Question 42

Angina Pectoris

Answer 42

paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort caused by transient (15 seconds to 15 minutes) myocardial ischemia that is insufficient to induce myocyte necrosis eitopatho: consequence of the ischemia induced release of adenosine, bradykinin, and other molecules that stimulate sympathetic and vagal afferent nerves

Question 43

stable or typical angina

Answer 43

most common form - has transient recurrent attacks associated with increased demand (PA) Due to reduction of coronary perfusion because of fixed stenosis Crushing or squeezing substernal pain, may radiate down the left arm Relieved by rest and vasodilators

Question 44

prinzmetal or variant angina

Answer 44

Occurs at rest, awakens the patient from sleep Associated with ST segment elevation on ECG, of transmural ischemia occurs due to coronary artery spasm producing transient squeezing chest pain Responds to vasodilators

Question 45

unstable (crescendo) angina

Answer 45

Pain that occurs with progressively increasing frequency and is precipitated with progressively less effort, often occurs at rest, and tends to be of more prolonged duration Induced by disruption of plaque with superimposed thrombosis and possibly vasospasm responds to vasodilators

Question 46

transmural infarctions

Answer 46

Involve the full thickness of ventricular wall in the distribution of a single coronary artery (STEMI) Usually associated with acute plaque changes and superimposed, completely occlusive thrombosis Can also occur with Cocaine abuse

Question 47

Subendocardial infarctions

Answer 47

Limited to the inner one third or at most one half of the ventricular wall also called NSTEMI Associated with diffuse stenosing coronary atherosclerosis or with prolonged hypotension (Global/Circumferential infarctions) May occur due to transient/partial arterial obstruction (Regional) Less serious than transmural infarction

Question 48

histology of MI | gross?

Answer 48

``` 0-12 hours = wavy fibers and early coagulative necrosis not much (gross) change ``` 12-24 = early neutrophil filtrate dark mottling 1-3 days = heavy neutrophil filtrate mottling (yellow/tan center) 3-7 days = macrophages appear center softening / hyperemic border 7-10 = granulation tissue max softening 10-14 days = collagen deposition grayish discoloration 2 months+ = dense scar scarring complete

Question 49

clinical features of MI

Answer 49

``` 1. chest pain retrosternal, crushing in nature may radiate the pain is persistent for >30 min (unlike angina) Not relieved by vasodilators or rest ``` 2. dyspnea 3. rapid weak pulse 4. diaphoresis, nausea and vomiting 5. silent MI (common in elderly)

Question 50

Troponins (I and T) after MI

Answer 50

Most sensitive and specific marker Normally not detectable in circulation Rises in 3-12 hrs peaks at 24 - 48 hrs. and persists for 7-10 days

Question 51

Creatine Kinase isoenzymes (CK-MB) after MI

Answer 51

A dimer composed of M & B subunits: MM, MB, BB CK-MB: most specific for the heart among the CKs Rises in 3-12 hrs Peaks at 18 - 24 hrs. and disappears by 48 - 72 hrs. Useful for detection of reinfarction

Question 52

complications of MI

Answer 52

1. ischemic (Extension of the infarction, Reinfarction, Angina) 2. Arrhythmic: most common cause of SCD (Myocardial irritability and conduction disturbances, Electrolyte imbalance, Hypoxia) 3. Embolic: mural thrombi (common in LV).. can lead to systemic emboli stroke ``` 4. mechanical contractile dysfunction papillary muscle dysfunction myocardial rupture ventricular aneurysm ``` 5. inflammatory pericarditis Dresslers’ syndrome (autoimmune)

Question 53

chronic ischemic heart disease

Answer 53

insidious onset of CHF in patients who have past episodes of MI or anginal attacks patho: cardiac decompensation owing to exhaustion of the compensatory hypertrophy of non- infarcted viable myocardium or severe coronary obstructive disease → diffuse myocardial dysfunction Arrhythmia, intercurrent MI are common and fatal gross: o Enlarged and heavy heart due to hypertrophy and dilation o Discrete gray white scars of healed previous infarcts o Patchy fibrous thickening of mural endocardium histo: o Myocardial hypertrophy o Diffuse subendocardial vacuolization - Myocytolysis o Scars of previously healed infarcts