Anti-HTN drugs

Question 1

HTN does what

Answer 1

Hypertension increases the risk of coronary thrombosis, stroke and renal failure
Controlling hypertension, which is generally asymptomatic, greatly improves prognosis
Blood pressure is an excellent surrogate marker for cardiovascular (CV) risk
Antihypertensive drugs prolong life and reduce CV risk

Question 2

Examples of anti-hypertensive drugs

Answer 2

● Drugs targeting the renin-angiotensin-
aldosterone system (RAAS)
● Calcium channel blockers (CCBs)
● Diuretics
● Hydralazine
● Drugs targeting the sympathetic nervous
system
● Nitrates

Question 3

Treatment strategy

Answer 3

-> A/CD rule
Angiotensin/ CCBs, Diuretics

-Thiazide diuretics and thiazide-like drugs
-Angiotensin Converting Enzyme Inhibitors (ACEIs) or
Angiotensin Receptor Blockers (ARBs)
-Long-acting Dihydropyridine Calcium Channel Blockers (CCBs)

Question 4

BP formula

Answer 4

Blood Pressure=
Cardiac Output (CO) [Stroke vol. x HR] X Total Peripheral Resistance (TPR) [big determinant: blood vessel radius]

Decrease BP:
Decrease TPR
Decrease CO
Decrease body fluid volume

Question 5

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs) Examples

Answer 5

enalapril, lisinopril, ramipril

Question 6

ACEIs mechanism of axn:

Answer 6

-Affect arteries and veins:
Reduce cardiac load and arterial pressure

-No effect on cardiac contractility
-Increased CO

Question 7

ACEIs
CLINICAL USES/ indications

Answer 7

● Hypertension
● Heart failure (HF)
● Post-MI
● High risk of ischemic heart disease
● Diabetic nephropathy
● Chronic renal insufficiency to prevent
progression

Question 8

ADVERSE EFFECTS
Of ACEIs

Answer 8

● Hypotension:
Especially after first dose and
In heart failure treated with loop diuretics, where RAAS is highly activated
● Dry cough (bradykinin accumulation)
Avoid in asthma to avoid confusion between drug- vs. asthma-related cough
● Hyperkalemia: drug-drug interactions
● Angioedema (potentially via bradykinin)
● Renal failure in renal artery stenosis
- Contraindication in renal artery stenosis and acute kidney injury
-Glomerular filtration maintained by ATII- mediated vasoconstriction (efferent arterioles)
-Hyperkalaemia may be severe due to reduced aldosterone secretion
-Reversible if caught early and ACEIs discontinued

Question 9

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)
Examples

Answer 9

-losartan, valsartan

Question 10

ARBs MoA

Answer 10

•Behave similarly to ACEIs in clinical practice
-Similar effectiveness on BP reduction and CV
outcomes

Similar side effect profile
Minus the cough
ACEIs and ARBs are contraindicated in pregnancy

Question 11

ACEIs and ARBs
Contraindications

Answer 11

pregnancy

Question 12

Low renin populations

Answer 12

●Elderly
●Afro-Caribbean descent

Question 13

CLINICAL USES
Of ARBs

Answer 13

•HTN especially in:
- young pts (have higher renin)
-Diabetic pts
- HTN complicated by LV hypertrophy

• Heart failure

•Diabetic neuropathy

Question 14

. RENIN INHIBITORS
Example

Answer 14

. aliskiren

Question 15

‘RENIN INHIBITORS
MoA

Answer 15

Lowers blood pressure but
Clinically somewhat unsuccessful

Only used if it’s options don’t work

Question 16

RENIN INHIBITORS

-Adverse effects

Answer 16

Diarrhea
Acute renal failure
Angioedema and severe allergic reactions (rare)

Question 17

RENIN INHIBITORS
Contraindications

Answer 17

Pregnancy like
ACEIs, ARBs, renin inhibitors

Question 18

-CALCIUM CHANNEL BLOCKERS (CCB)

Effects on blood vessels

Answer 18

•Generalized arterial/arteriolar dilatation
•Reduce blood pressure
-Can be offset by reflex increase in sympathetic (SNS) activity secondary to vasodilator action
•Little effect on veins
•Cause coronary vasodilation
-Useful in variant angina

Question 19

Effects on heart
(CCB)

Answer 19

•Decrease heart rate and force of contraction
•May cause AV block and cardiac slowing by effects on conducting tissue
•May excessively decrease CO
(Pts. W/ ❤️ failure CANNOT take these)

Question 20

‘3 main classes of Ca2+ channel blockers with preferential action locations:

Answer 20

•vessels vs. heart
•Bind the a1 subunit in LTCC
•Show ‘use dependence’

Question 21

Types of CCB

Answer 21

1. DIHYDROPYRIDINES (nifedipine, amlodipine)
2. Phenylalkylamine (Verapamil)
3. BENZOTHIAZEPINES (Diltiazem)

Question 22

DIHYDROPYRIDINES Examples

Answer 22

nifedipine, amlodipine

Question 23

DIHYDROPYRIDINES
MoA

Answer 23

•Act mainly on arterial resistance vessels (arterioles) •Produce vasodilation
● Lower TPR which leads to Lower afterload on heart
•Typically cause reflex tachycardia
•Do not worsen CV mortality in severe but stable congestive heart failure

Question 24

Phenylalkylamine example

Answer 24

Verapamil

Question 25

Phenylalkylamine MoA

Answer 25

•Acts mainly on cardiac myocytes
• lower HR and lower force of contraction
● Strongest inotropic effects by blocking
phase 2 plateau

Question 26

Phenylalkylamine CI

Answer 26

-Contraindicated in HF

Question 27

Phenylalkylamine clinical uses

Answer 27

Clinical uses: angina, arrhythmias (not in the presence of HF), hypertension

Question 28

BENZOTHIAZEPINES
Ex.

Answer 28

Diltiazem

Question 29

BENZOTHIAZEPINES MoA

Answer 29

•Acts on both cardiac and vascular myocytes
•Little or no change in heart rate

Question 30

BENZOTHIAZEPINES clinical uses

Answer 30

Clinical uses: angina, hypertension
Not in the presence of HF

Question 31

DIHYDROPYRIDINES

Clinical uses:

Answer 31

Clinical uses: angina (dilation of coronary arteries), hypertension, Raynaud phenomenon Clevidipine/nicardipine: hypertensive crisis or urgency (IV)

Question 32

Adverse effects of CCB -> Dihydropyridines

Answer 32

Flushing and headache (vasodilator action)
Reflex tachycardia
Contraindicated in unstable angina
Peripheral edema (ankle swelling)

Question 33

ADVERSE EFFECTS

Verapamil

Answer 33

•Constipation
-Probably due to effects on calcium channels in GI nerves or smooth muscle
•Effects on cardiac rhythm (e.g. heart block) and force of contraction (e.g. worsening heart failure)
-Contraindication
-Should not normally be co-prescribed with beta-blockers (can cause AV block)

Question 34

Clinical uses of calcium antagonists

Answer 34

1.Dysrhythmias (verapamil):
- slow ventricular rate in rapid atrial fibrillation
- to prevent recurrence of SVT
2. HTN: usually a dihydropyridine drug (amlodipine)
3. To prevent angina (dihydropyridine/diltiazem)