Anti-hypertensives I

Question 1

Which anti-hypertensive drugs work in the indiciated areas of the body below?

Answer 1

Sympatholytics (i.e. alpha receptor agonists): clonidine

Drugs that:

1. Decrease cardiac output: Beta blockers (propanolol, metaprolol etc); Non-dihydropyridine CCBs
2. Vascular smooth ms dilation: (a lot, see below)
3. Na+/water elimination: RAAS inhibitors, diuretics

Question 2

Study this slide

Answer 2

Question 3

What is the effect of pre-synaptic adrenergic agonists on NE release?

Answer 3

Presynaptic adrenergic agonists: referring to alpha 2 agonists >> cause decreased NE release

Question 4

What is the effect of post-synaptic antagonists on hypertension regulation?

Answer 4

Post synaptic antagonists: alpha and beta blockers >> decrease HTN (various effects)

Question 5

___ is a sympatholytic (alpha 2 agonist) drug that acts on A2 receptors in the CNS to reduce HR and BP

Answer 5

Clonidine is a sympatholytic (alpha 2 agonist) drug that acts on A2 receptors in the CNS to reduce HR and BP

**also used in neuropsychiatric disorders, and can cause drowsiness and sedation**

Question 6

Once started, clonidine should not be abruptly discontinued. Why is that?

Answer 6

Abrupt discontinuation results in withdrawal syndrome: rebound hypertension and tachycardia (can be life-threatening)

Question 7

___, ___ and ___ are anti-HTNs used in pregnancy

Answer 7

Methyldopa, nifedipine and labetalol are anti-HTNs used in pregnancy

Question 8

How do Beta blockers work?

Answer 8

Beta blockers: basically block increased intracellular Ca2+ and subsequent contractility by blocking the beta receptors

Question 9

Fill in the blanks

Answer 9

Question 10

Why are the effects of beta blockers not long term?

What is unique about the beta blocker Nebivolol?

Answer 10

Effects aren’t long term b/c there are compensatory responses in peripheral vasculature

Nebivolol promotes NO release (which you will recall is a potent vasodilator)

Question 11

Fill in the blanks

Answer 11

**know that non selective beta blockers aren’t first line for HTN because they also beta 2 effects**

Question 12

Fill in the blanks

Answer 12

Question 13

Fill in the blanks

Answer 13

Question 14

What are the side effects of beta blockers in pts with: restrictive airway disease (COPD,asthma), peripheral vascular disease, Type 2 diabetes mellitus?

Answer 14

Restrictive airway disease: asthma or COPD exacerbation

PVD: unopposed alpha 1 vasoconstriction (can worsen symptoms)

Diabetes mellitus: Hypoglycemia

Question 15

Beta blockers are contraindicated in which conditions? (5)

Answer 15

(Symptomatic) Bradycardia

(Symptomatic) Hypotension

(Severe) restrictive airway disease

Cardiogenic shock (remember, volume ok but pump is broken)

2nd or 3rd degree heart block

Question 16

Describe the mechanism of action of calcium channel blockers

Answer 16

CCBs block L type calcium channels on vasc sm muscle, cardiac myocytes or SA/AV nodal cells

Question 17

What are the effects of CCBs in the cells indicated below?

Answer 17

**see below**

Question 18

Which CCBs would you use for the scenarios below?

Answer 18

**see below**

Question 19

What are the classes of calcium channel blockers?

Answer 19

Dihyropyridines - ipine- drugs

Non-dihydropyridines

Question 20

What are the 2 main Dihydropyridine CCBs?

**Fill in the blanks**

Answer 20

Amlodipine and Nifedipine (remember the big knife in sketchy. Can be used in pregaz)

Question 21

What are the 2 main non-dihydropyridines?

Answer 21

Diltiazem and Verapamil (has the most cardio-depressive effects)

Question 22

What are the adverse effects of dihydropyridines (3)?

What are the adverse effects of non-dihydropyridines (3)?

Answer 22

**see below**

Question 23

Describe the mechanism of action of nitrovasodilators

Answer 23

**remember that NO is a vasodilator thru decreased calcium for muscle contraction >> vasodilation**

Question 24

What is a potent nitrovasodilator used for HTN treatment?

Answer 24

Na+ nitroprusside

Question 25

What are the effects low vs high NO concentrations/i.e which vessels (large/small/veins/arteries) get dilated at these concentrations?

Answer 25

* Low NO concentrations vasodilate veins and coronary arteries * High NO concentrations are required for vasodilation of large arteries

Question 26

How does nitroglycerin work as a vasodilator?

Answer 26

**Nitroglycerin** is broken down by **Aldehyde dehydrogenase-2** first and then it forms NO (so indirectly contributes NO, compared to Na+-nitropusside which directly gives NO)

Question 27

Why wouldn't you use a PDE inhibitor concurrently with a nitrovasodilator?

Answer 27

Phosphodiesterase normally breaks down cGMP. If you use a drug that inhibits PDE at the same time as using a nitrovasodilator, that’ll cause severe hyPOtension

Question 28

What are the clinical indications for nitrates?

Answer 28

Chest pain/angina Acute coronary syndromes Acute decompensated heart failure (mainly nitroglycerin + long acting nitrates are indicated in BP)

Question 29

A challenge with using nitrates for BP is the development of nitrate tolerance. What are 4 mechanisms thru which tolerance develops?

Answer 29

\*\*see below\*\*

Question 30

What are 3 strategies to combat nitrate tolerance?

Answer 30

Nitrate-free interval (6-8 hours “off” each day) Concomitant use of an antioxidant (e.g., hydralazine) Concomitant use of neurohormonal antagonists \*\*think about how tolerance develops. your interventions should be addressing that\*\*

Question 31

What is the mechanism by which sodium nitroprusside has adverse effects?

Answer 31

Major adverse effect on Na+-nitropusside is mediated by **accumulation of toxic metabolites** Sodium nitroprusside is broken down to **cyanide (toxic)** which is **conjugated by the liver** to form **thiocynate (also toxic)** which is then **renally excreted**. Pts with liver or kidney disease should not be on nitrates for extended periods for this reason. \*\*can be fixed with Hydroxycobalamin/Na-thiosulfate/nitrites\*\*