Hypertension Drugs 1 Flashcards
How is blood pressure related to risk of stroke and CV disease?
Risk rises exponentially with increasing blood pressure
What is the distribution of hypertension within the general population?
hypertension exhibits normal distribution
Who gets hypertension the most?
older women
What percentage of US adults has hypertension?
30.4% about 67 million people
What percentage of US adults with hypertension are under good control?
46.5% about 31 million people which means that 53.5% are uncontrolled
What percentage of US adults with uncontrolled hypertension are unaware they have it?
about 40%
What adverse CV events can be associated with hypertension?
heart failure myocardial ischemia & infarction stroke aortic aneurysm & dissection retinopathy nephrosclerosis renal failure
According to JNC8, what is the target BP for people >60 years?
<90
According to JNC8, what is the target BP for people 18 years with CKD, and >18 years with diabetes?
<90
What are the 4 major classes of anti-hypertensive drugs?
- vasodilators
- adrenergic affecting agents
- RAS affecting agents
- diuretics
How do vasodilators in general decrease BP?
- decrease vascular tone which decreases peripheral resistance
- causes degrees of increased SNS output usually increasing heart rate
What are some direct arterial vasodilators?
- Hydralazine
- Minoxidil
- Diazoxide
- Nitroprusside
- Fenoldopam
Arterial vasodilators cause direct smooth muscle relaxation reducing perfusion pressure which activates what reflexes?
– baroreceptor activation: compensatory increase in sympathetic outflow; tachyphylaxis can cause loss of antihypertensive effect
– Reflex release of renin (which can be blocked by beta-blockers)
What is hypertensive crisis?
BP> 180/120
needs to be brought down gradually
What is hypertensive urgency?
elevated BP with no acute or progressing target-organ injury
What is hypertensive emergency?
high BP with acute or progressing target-organ damage
Hypertensive emergency can result in what?
encephalopathy, intracranial hemorrhage, acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, unstable angina, eclampsia
What is the MOA of nitric oxide donors?
NO binds receptor and causes increase in cGMP/protein kinase G
Do nitric oxide donors only work on arteries?
No, some venous component
Which nitric oxide donor can cause cyanide toxicity?
nitroprusside
General adverse effects of direct arterial vasodilators?
– sodium / water retention
– tachycardia / angina
Adverse effect of hydralazine?
Hydralazine can cause lupus-like syndrome
Adverse effect of minoxidil?
Minoxidil can cause hair growth
How could you counteract the fluid retention and reflex tachycardia?
Use with diuretic (preferably thiazide) & β-blocker
In general, how do Ca channel blockers affect hypertension?
- decrease vascular tone which decrease peripheral resistance
- there is a small increase in heart rate due to SNS
What are some Ca channel blockers?
- Nifedipine
- Diltiazem
- Verapamil
- Amlolodipine
What are some non-dihyrdopyridines?
diltiazem & verapamil
What are some dihyrdopyridines?
amlodipine, felodipine & nifedipine
Adverse effects of all Ca channel blockers?
flushing & headaches
Ca channel blockers that cause negative inotropic effect?
verapamil > diltiazem > nifedipine
Ca channel blockers that cause constipation?
verapamil > diltiazem or nifedipine
Ca channel blockers that cause decreased AV conduction?
verapamil = diltiazem > nifedipine
Ca channel blockers that cause edema?
nifedipine > verapamil or diltiazem
Which adrenergic receptors on the heart increase contractility and HR?
beta-1
Which adrenergic receptors on arterioles causes vasoconstriciton?
alpha-1
Which adrenergic receptors on arterioles cause vasodilation?
beta-2
Which adrenergic receptors on the lungs cause bronchodilation?
beta-2
Which adrenergic receptors on the kidneys cause increased renin?
alpha-1 and beta-1
In general, how to mixed alpha blockers lower blood pressure?
- block alpha-1 decreasing vascular tone which decreases peripheral resistance
- block alpha-2 decreasing venous tone decreases venous return which decrease CO
- large increase in HR due to SNS
What are alpha-1/alpha-2 blocker drugs?
Phenoxybenzamine & Phentolamine
MOA of alpha-1/alpha-2 blocker drugs?
inhibit smooth muscle catecholamine uptake in peripheral vasculature: vasodilation & BP lowering
In general, how to alpha-1 specific blockers lower blood pressure?
- block alpha-1 decreasing vascular tone which decreases peripheral resistance
- smaller increase in HR due to SNS
What are some alpha-1 specific blockers?
- Prazozin
- Terazosin
- Doxazosin
Benefits of being alpha-1 specific?
- Smaller increase in heart rate
- Do not stimulate renin release
- Does not block α2 – thus NE can inhibit its own release
Alpha-1 blockers have a first dose effect, what’s that?
– orthostatic hypotension
– transient dizziness, faintness, palpitations, syncope within 1 to 3 hours of 1st dose
– reflex tachycardia
– first dose at bedtime to minimize effect
A mixed α1 /β Blocker can help minimize first dose effect, what’s up with that?
– α1 competitive inhibitor
– β1& β2 competitive inhibitor
– Mild orthostatic hypotension & headaches
In general, how do beta-blockers lower blood pressure?
- inhibit beta-1 on kidneys decreases renin decreasing ATII decreases vascular tone decreasing peripheral resistance
- inhibit beta-1 on heart decreasing rate which decreases CO
Stimulating beta-1 receptors does what?
– heart, kidney
– stimulation increases HR, contractility, renin release
Stimulating beta-2 receptors dose what?
– lungs, liver, pancreas, arteriolar smooth muscle
– stimulation causes bronchodilation & vasodilation
– mediate insulin secretion & glycogenolysis
What are some beta-blocker drugs?
- Propranolol - β1 / β2
- Metropolol – β1
- Atenolol – β1
- Labetalol – β1 / β2 / α1
Beta-blockers work best in young adults and work well in older adults in combo with what?
diuretics
Which beta-blockers are cardio selective?
Metropolol & Atenolol have greater affinity for β1 than β2 receptors
– inhibit β1 receptors at low to moderate dose
– higher doses block β2 receptors
Cardio selective beta-blockers are safer for who?
Safer in patients with bronchospastic disease, peripheral arterial disease, diabetes – may exacerbate bronchospastic disease when selectivity lost at high doses
Generally preferred β-blockers for hypertension?
Metropolol & Atenolol
Potential adverse effects of beta blockers?
– Glucose intolerance, masked hypoglycemia
– Bradycardia, dizziness
– Bronchospasm
– Increased triglycerides and decreased HDL
– CNS: Depression, fatigue, sleep disturbances
– Reduced C.O., exacerbation of heart failure
– Impotence
– Exercise intolerance
