Hypertension: Pharmacology - Imig Flashcards Preview

M2 Cardiovascular > Hypertension: Pharmacology - Imig > Flashcards

Flashcards in Hypertension: Pharmacology - Imig Deck (46):
1

Explain the distribution and relative risk of blood pressure.

Blood pressure has a normal distribution; those with elevated BP have exponentially increased risks of stroke and CVD.

2

Which patient demographic is at highest risk of hypertension (think age, gender)

Post-menopausal women.

3

About 25-30% of US adults have hypertension. About how many of those are not controlling their hypertension? Why?

Just over half are uncontrolled, of which many are simply unaware of their hypertension.

4

Vasodilators

Describe how they decrease blood pressure.

Give some examples.

Vasodilators

Directly decrease vascular tone via multiple pathways (NO>>cGMP, K+-ATPase, dopamine antagonism)

Hydralazine, Nitroprusside, Diazoxide, Minoxidil, Fenoldopam

5

Why are direct arterial vasodilators often coadministered with a beta-blocker?

The beta-blocker will counter the resulting baroreceptive reflex (tachycardia, renin release).

6

What defines a hypertensive crisis?

Distinguish between hypertensive urgency and emergency.

How are they handled?

BP >180/120mm Hg.

Urgency features no organ injury. Emergency does (eg encephalopathy, hemorrhage, LV failure, eclampsia, UA, dissecting aneurysm)

Reduce blood pressure (GRADUALLY).

7

Fill in the blank:

Nitroprusside is a vasodilator that acts mainly on the ____ circulation, producing NO to activate ____. Its major toxicity is ____, made worse by ____.

Nitroprusside is a vasodilator that acts mainly on the venous circulation, producing NO to activate GC/cGMP. Its major toxicity is cyanide toxicity, made worse by renal or hepatic injury.

8

What are the side effects of direct arterial vasodilators? (general AND specific)

With what should they be co-administered?

General: Sodium/fluid retention, tachycardia/angina.

Specific: Hydralazine causes lupus-like syndrome, Minoxidil causes hair growth.

Counteract the general SEs with diuretics and beta-blockers.

9

Calcium Channel Blockers

Describe how they decrease blood pressure.

Give some examples.

Calcium Channel Blockers

They decrease vascular tone, and sometimes decrease heart chronotropy/inotropy.

Nifedipine, Amlodipine, Diltiazem, Verapamil.

10

Distinguish between the mechanisms of actions of DHPs and non-DHP CCBs.

Describe their side effects.

DHPs act more on vascular tissue, while non-DHPs act more on heart tissue (decrease HR and AVN conduction).

Both cause flushing and headaches. nonDHPs cause constipation and --Inotropy/AVN conduction, while DHPs (mostly nifedipine) cause edema and "refractoriness".

11

Try to recall the locations and effects of the adrenergic receptors: α1, α2, β1, β2.

α1 in arterioles (vasoconstriction of skin & splanchnics) & kidneys (increased renin)

α2 in many presynaptic terminals (negative feedback)

β1 in heart (++ino/chrono), kidneys (increased renin)

β2 in lungs (bronchodilation)

12

a1/a2 Blockers

Describe how they decrease blood pressure.

Give some examples.

a1/a2 Blockers

Decrease vascular tone by blocking SNS constriction.

Phenoxybenzamine, Phentolamine.

13

How are a1 blockers superior to a1/a2 blockers?

Do they competitively or noncompetitively block a1?

When should they be administered?

Blockage of a2 blocks negative feedback via the presynaptic receptors; a1 blockers avoid this (net better SNS blocking)

Competitive.

At bedtime to minimize SEs.

14

a1 Blockers

Give some examples.

Name their side effects (general and specific)

a1 Blockers

Prazosin, Terazosin, Doxazosin.

First dose effect results in orthostatic hypotension, dizziness/faintness, palpitations, syncope. Still some reflex tachycardia.

15

ß-Blockers

Describe how they decrease blood pressure.

Give some examples.

ß-Blockers

Block stimulation of renin secretion, as well as heart inotropy/chronotropy.

Propranolol, Metoprolol, Atenolol, Labetalol... about 10 others.

16

Recall some of the side effects of beta blockers.

What do most of these result from?

Which beta blockers avoid these effects?

Glucose intolerance, masked hypoglycemia, bronchospasm, altered lipid profile, CNS depression, impotence, decreased CO/HR...

Many of these result from ß-2 blockage.

The cardioselective beta blockers (metoprolol, atenolol) do not have these effects at low dosage. Better for those with bronchospasm, diabetes, PAD...

17

Are beta blockers indicated for patients with high-renin HTN?

How does age affect beta-blocker usage?

Yes; beta blockers are much more effective in these patients than in those with low renin.

Beta blockers are less effective in older adults, and are best paired with diuretics then.

18

What category do labetalol and carvedilol fall under?

What are their side effects?

These are mixed a1/ß blockers. (competitive inhibitors)

MIld orthostatic hypotension & headaches.

19

Central a2 Agonists

Describe how they decrease blood pressure.

Give some examples.

Central a2 Agonists

Stop SNS outflow from the vasomotor center (vagal tone predominates).

Clonidine, Guanabenz, a-methyldopa.

20

What are the side effects of central a2 agonists? (general & specific)

General: Sodium/fluid retention, depression, orthostatic hypotension/dizziness, rebound upon discontinuation.

Specific: Clonidine has anticholinergic SEs, Methyldopa can cause hepatitis and (rarely) hemolysis.

21

Neuronal/Ganglionic Blockers

Describe how they decrease blood pressure.

Give some examples.

Neuronal/Ganglionic Blockers

Stop SNS outflow, this time at the nerve synapse. Multiple mechanisms (usually block release).

Guanethidine, Guanadrel, Reserpine, Trimethaphan

22

Describe the side effects of neuronal/ganglionic blockers (specific & general).

General: Decreased CO/HR, diarrhea, fluid/sodium retention (countered with diuretic).

Specific: Reserpine causes sedation/depression and increased gastric acid secretion.

23

Describe some mechanisms by which diuretics produce vasodilation

  • decreased Na/water in vessel wall
  • PGI2 and NO release
  • Vascular K channel activation
  • Decrease sensitivity to NE
  • Increase Na-Ca exchange

24

Describe the mechanism of the hypotensive effects of diuretics

Exact mechanism unknown

initial: BP drop caused by diuresis

later: chronic hypertensive effect - EC and plasma volume return to near baseline, but PVR is lower than baseline.

25

What are some adverse effects of diuretics?

  • electrolyte disturbances
  • hyperglycemia
  • hypotension, orthostasis
  • lipid abnormalities
  • photosensitivity
  • ototoxicity
  • hyperuricemia (gout flares)

26

Describe the general class/mechanism of:

  1. Aliskiren
  2. Lisinopril
  3. Losartan
  4. Spironolactone

  1. Blocks conversion of angiotensinogen to angiotensin I
  2. ACE inhibitor
  3. ARB
  4. aldosterone receptor inhibitor

27

Where is ACE (angiotensin-converting enzyme) typically found?

Many tissues, primarily endothelial cells and blood vessels

28

Besides converting antiotensin I to angiotensin II, what are some other roles of ACE?

block bradykinin degradation

stimulate synthesis of vasodilating substances such as PGE2 and prostacyclin

29

What are some adverse effects of ACE inhibitors?

  • cough (bradykinin?)
  • angioedema -> cease therapy immediately (and ARBs)
  • hyperkalemia (especially CKD and DM patients)
  • neutropenia, agranulocytosis, proteinuria, glomerulonephritis
  • acute renal failure

30

What are some adverse effects of ARBs? What adverse effect is observed less often (or less severely) than with ACE inhibitors?

  • orthostatic hypertension
  • renal insufficiency
  • hyperkalemia

Less cough than ACE inhibitors (ARBs do not block the breakdown of bradykinin)

31

Compare the roles of AT1 vs. AT2

AT1 = 'bad'

  • vsoconstriction
  • vascular proliferation
  • aldosterone secretion
  • cardiac myocyte proliferation
  • increased sympathetic tone

AT2 = 'good'

  • vasodilation
  • antiproliferation
  • apoptosis

32

Approximately how long does it take ARBs to reach their maximum effect (model: Losartan)

~4-6 weeks

33

What are some adverse effects of aliskiren?

  • orthostatic hypotension
  • hyperkalemia

 

34

ACE inhibitors and ARBs are contraindicated in what patient populations?

  • Can cause kidney failure in: severe bilateral renal artery stenosis or severe stenosis to solitary kidney
  • Pregnant women

35

Name some drugs that commonly adversely interact with ACE inhibitors and ARBs

  • Medications promoting hyperkalemia
  • Medications sensitive to changes in serum K+
  • Other antihypertensive medications (excessive additive effects)
  • NSAIDs

36

Losartan (and other ARBs or ACE inhibitors) are commonly combined with which other drug to produce a greater antihypertensive effect?

HCTZ (or other thiazide diuretic)

37

Describe the basic hypertension treatment algorithm described by JNC7

  • Attempt lifestyle modifications
  • If still not at goal (<140/90 mmHg or <130/80mmHz for CKD or DM): drug choices
    • with compelling indications - use compelling indication drugs
    • without compelling indications:
      • Stage 1 hypertension (SBP: 140-159 or DBP 90-99): thiazides, consider ACEI, ARB, BB, CCB, or combo
      • Stage 2 hypertension (SBP>160 or DBP>100): two-drug combo (thiazide + ACEI/ARB/BB/CCB)

38

Describe some lifestyle modifications typicall recommended to decrease hypertension

  • reduce weight
  • DASH eating plan
  • dietary sodium restriction
  • increase physical activity
  • reduce alcohol consumption

39

Name the physiological parameters that require monitoring for each:

  • Diuretics
  • beta-blockers
  • RAA drugs
  • CCBs

  • Diuretics: blood pressure, BUN/SC, serum electrolytes, uric acid (thiazides)
  • BB: blood pressure, heart rate
  • RAA: blood pressure, BUN/SC, serum K+
  • CCB: blood pressure, heart rate

40

Describe the antihypertensive drug considerations of each of the following special populations:

  1. African Americans
  2. Left ventricular hypertrophy
  3. Elderly
  4. Pregnancy
  5. Children and adolescents

  1. Angioedema 2-4x higher prevalance. Response to diuretics + CCB is generally better than ACEI, ARB, or BB.
  2. LVH: aggressive control regresses LVH. However, minoxidil and hydralazine do not help
  3. Elderly (w/ isolated systolic HTN): thiazides and CCBs may be better tolerated
  4. Pregnancy: no ARBs or ACEI. Use methyldopa, BB, and vasodilators (such as hydralazine)
  5. Children/adolescents: no ARBs or ACEI in pregnant or sexually active girls

41

What drug class should always be used as a part of combo therapy for hypertension (unless contraindicated)?

thiazide diuretic

42

Define resistant hypertension

failure to achieve BP goal on full doses of a 3-drug antihypertensive regimen which includes a diuretic

43

Which drug, used in hypertensive emergencies, carries a risk of thiocyanate and cyanide toxicity?

Sodium Nitroprusside

44

Acute heart failure specifically contraindicates what drug(s) commonly used in hypertensive emergencies?

Nicardipine, labetalol

also: caution with clevidipine

45

Which hypertensive emergency drug should be used with caution in patients with glaucoma?

What are the caution(s) for Sodium Nitroprusside?

Fenoldopam

High intracranial pressure, azotemia, CKD

46

What drug is specifically indicated for eclampsia?

Hydralazine