Antihypertensive Meds- Austin

At normal HR, MAP= _______DBP + _____SBP

At normal HR, MAP= _______DBP + _____SBP

MAP= 2/3 DBP + 1/3 SBP

EDV is also called…

preload

Definition of Inotrophy

muscle state of the heart in the absence of fluid

• Think: how much your heart can bench press

Definition of venous compliance/ venous tone:

how good veins are at returning blood to the heart

3 mechanisms in our body that regulation bp:

1. baroreceptors

2. the kidney

3. circulating hormones

Hypertension is long term bp elevation of ≥____/_____

≥130/80

Why is hypertension also known as the “silent killer”?

bc it’s usually asymptomatic

What is the difference between primary and secondary hypertension?

primary- cause is genetic/non modifiable factors + environment/lifestyle factors

secondary- bc of an underlying condition or drug/alcohol use

What are 4 different strategies we can use to decrease bp?

• just an FYI

1. decrease blood volume

2. dilate blood vessels

3. sympatholytics (antagonists)

4. inhibit RAAS system

Thiazide Diuretics MOA

• inhibit reabsorption of Na/Cl in the distal tubule

• increase Ca reabsorption

Thiazide diuretics have a potential to cause hypersensitivity/allergic reactions bc of what group?

sulfonamide

Describe pregnancy categories (A,B,C,D,X):

A- pretty safe

B- probably safe

C- conflicting responses or not enough data

D- potentially harmful

X- NOT safe

cardiomyopathy definition:

Cardiomyopathy is a term used to describe diseases of the heart muscle. It refers to a group of conditions that affect the structure and function of the heart muscle, making it harder for the heart to pump blood effectively.

CCB MOA:

block L-type voltage-gated Ca²⁺ channels of cardiac muscle or blood vessels

Basically, CCBs stop/decrease ______________ to decrease SV and MAP.

contraction

CCBs are put into what 2 categories?

DHPs and non-DHPs

DHPs are selective for _______ muscle.

arterial smooth muscle

non-DHPs are selective for ________ muscle.

cardiac muscle

Example of 1st, 2nd, and 3rd generation DHPs:

1st- Nifedipine

2nd- Felodipine

3rd- Amlodipine

2 Examples of non-DHPs:

1. Diltiazem

2. Verapamil

DHPs bind __________ the cell, and non-DHPs bind __________ the cell.

a. inside, inside

b. outside, outside

c. inside, outside

d. outside, inside

d. (DHPs-outside, non-DHPs- inside)

Are DHPs or non-DHPs typically used for HTN?

DHPs

Non-DHPs have a risk of potential drug interactions due to being substrates of CYP_____ and CYP_____.

CYPD6 and CYP3A4

Non-DHPs are BAD in what condition?

Heart Failure

How do non-DHPs affect the heart?

• decrease HR

  • inhibit/slow Ca²⁺ dependent APs in the SA node

• decrease force of contraction

  • inhibit Ca²⁺ channels in the myocardium

When would be a situation where we would use a non-DHP for HTN? (we don’t normally use non-DHPs w/ HTN tho)

HTN w/ concurrent arrhythmia

• Ex: if you have HTN and tachycardia

What is the pharmacophore for DHPs?

1,4-dihydropyridine

How do DHP CCBs effect smooth muscle, contraction, PVR, and afterload?

• RELAX smooth muscle

• reduce contraction, PVR, and afterload

ADRs of DHPs and non-DHPs:

DHPs: flushing, tachycardia

Non-DHPs: AV block, constipation, bradycardia, caution in cardiomyopathy

Both: HA, hypotension, peripheral edema

CCBs are pregnancy category ______.

(A,B,C,D,X)

C

Do CCBs effect kidney function?

no

C

C

A

What stimulates the RAAS (Renin-Angiotensin-Aldosterone System)?

In general: decrease in BP

More specific:

1. ↓ in BP

2. ↓ in Na delivery to distal tubule

3. activation of adrenergics

What are the steps of the RAAS system? (Starting with renin release and ending with increasing BP)

1. renin release

2. Angiotensinogen to Ang I (using renin)

3. Ang I to Ang II (using ACE enzyme)

4. Ang II stimulates a variety of pathways- aldosterone secretion, Na and water reabsorption, K excretion, vasoconstriction in vessels

5. increase BP

What receptor does Ang II bind to?

AT₁ receptor

The effects of Ang II are opposite of what hormone?

ANP

Bradykinin is an inflammatory mediator and ______________.

vasodilator

Prostaglandins play an important role in the…

dilation of afferent arterioles

ACTH (Adrenocorticotropic hormone) operates INDEPENDENTLY of SNS and is another pathway that can…

stimulate aldosterone synthesis

BOXED warning of Renin Inhibitors:

Fetal Toxicity

What is the generic name of the only renin inhibitor on the market?

aliskiren

MOA of Aliskiren:

prevents conversion of Angiotensinogen to Ang I

ANY drug that inhibits or deals with the RAAS should not be used during _______________.

pregnancy

Warnings of Aliskiren/Renin Inhibitors:

• hyperkalemia

• angioedema

• hypotension

• decreased renal fxn

Drug Interactions of Aliskiren/Renin Inhibitors:

• NSAIDs

• caution with ACE inhibitors (we know not to combine RAAS drugs)

• K+ sparing agents

Boxed warning of ACEIs and ARBs:

FETAL TOXICITY

ACEIs generic names end in “-________”

-pril

MOA of ACEIs:

General: inhibit ACE enzyme conversion of Ang I to Ang II, and block bradykinin degradation

More specific: bind Zn²⁺, arginine residue, and 2 hydrophobic pockets of ACE to inhibit the ACE enzyme

Do ACEIs, Renin Inhibitors, ARBs typically cause reflex tachycardia?

no

What side effect from ACEIs are due to bradykinin?

bradykinin not degraded so…

• cough

• angioedema

ADRs of ACEIs:

• hypotension

• hyperkalemia

• N/V/D

• HA

• dizzy

• decline in renal function

Drug Interactions of ACEIs:

similar to renin inhibitors

• other hypotensives

• NSAIDs

• diuretics

Most ACE inhibitors and ARBs are metabolized by phase II _____________.

conjugation

3 general categories of ACEIs:

1. dicarboxylate- most common

2. sulfur containing

3. phosphate containing

How do ARBs effect the RAAS system?

competitive antagonists of AT₁ receptors

ARBs have a less risk of ______________ compared to ACEIs.

angioedema

ADRs of ARBs:

• angioedema

• hyperkalemia

• hypotension

• dizzy

• HA

Drug Interactions of of ARBs:

identical to ACEIs and Renin Inhibitors

• other hypotensives

• diuretics

• NSAIDs

B