11 05 2014 Anti-hypertensive drugs Flashcards
what are the 4 classes of drugs used to treat hypertension
- Diuretics
- Sympatholytics
- Vasodilators
- Drugs that interfere with renin-angiotensin system
what are factors that increase cardiac output
- Excess sodium intake – could be due to an altered renal sodium retention
- this increases fluid – increases preload – increases CO - Renin - RAAS – Increase sodium retention
- SNS increases HR and contractility
CO = HR X BP
What are the targets of Antihypertensive drugs
- sodium/ Plasma volume
- RAAS
- SNS
- Vascular Smooth muscle
Thiazide diuretics (mechanism)
target Na+ -Cl- exchanger (NCC) symporter – inhibit reabsorption of Na+ in distal tuble
Affects Na+/K+ pump and now K+ is excreted
= hypokalemic statuses
Hydrochlorothiazide
Chlorthalidone
Loop Diuretic
Target Na+ K+ 2Cl- symporter in thick ascending limb of nephron
Block reabsorption of Na+
Very potent but very short lived
Ex. Flurosemide
- reserved for CHF or resistant edema
Adverse effects of Thiazide/ Loop Diuretic Therapy
- Volume depletion (hypotension and decrease GFR)
- Hypokalemia ( increase in distal Na+/K+ exchanger)
- Hyponatremia
- Metabolic Alkalosis
- Increase in uric acid — Gout
- Hyperglycemia
- K- sparing agents : hyperkalemia
- Gynecomastia/ sexual dysfunction ( spironolactone –potassium sparing diuretic)
Hydrochlorthiazide
most common drug used – thiazide
Good for volume-overloaded/ salt depedent/ low renin HTN
Direct Vasodilators
- calcium channel blockers
- Hydralazine and minoxidil
Adverse effects: fluid retention, tachycardia
-reflex increase in SNS so pair with beta-blocker
Calcium channel blockers
- target
- any AE?
- names of drugs
- interesting fact about two drugs?
Target voltage-sensitive L-Type canals
- affect Ca2+ in smooth muscle, AV and SA node
= relaxation
Metabolically neutral : no effects on glucose
No renal, CNS or pulmonary AE.
AE: edema, flushing, lightheadedness, CONSTIPATION at all doses.
- Bradycardia
- Skin rash is common
Diltiazem
Verapamil
Nifedipine ( Amlodipine)
Nicardipine
- Diltiazem and verapamil inhibit hepatic P450 enzymes
Hydralazine
Oral and IV
Short acting
Directly relaxes vascular smooth muscle of pre capillary resistance vessels
Potential for lupus syndrome w/ pericarditis
Minoxidil
Very potent oral agent
AEs include hypertrichosis, pericardial effusions, massive fluid retention
Directly relaxes vascular smooth muscle of pre capillary resistance vessels
Nitroprusside
Release NO = dilates arterioles and venues (decrease preload and after load)
Cyanide toxicity
Useful in severe or refractory HTN – pulmonary edema emergency
Alpha receptor Antagonist
Inhibit vasoconstriction of NE
Decrease total peripheral resistance (TPR) but with LESS tachycardia
Adverse effects: postural hypotension, headache, edema
Phentolamine
(IV)
Nonselective alpha receptor antagonists
Adverse Effects: postural hypotension, headache, edema
Phenoxybenzamine
Oral
Nonselective alpha receptor antagonist
Adverse Effects: postural hypotension, headache, edema
Prazosin, terazosin, doxazosin
Alpha 1 selective antagonists
oral
Also used for symptoms of prostatic hypertrophy.
Blockade of peripheral arterioles and venues
Toxicity: Dizziness, headaches,lassitude
CNS- acting Sympathetic inhibitor
Alpha 2 receptor antagonists in the medullary brainstem
Act in CNS to decrease outflow
Clonidine
Alpha methyldopa
Clonidine
Oral and transdermal (patch)
Onset 30-60 min – useful for HTN urgencies
AE: sedation, dry mouth, rebound BP (increase)
Sudden withdrawal can result in sudden hypertensive crisis
Alpha methyldopa
Oral and IV
AE: sedation ,hepatitis, and coombs pos hemolytic anemia
*** PREGNANCY ASSOCIATED HTN
Effects of a beta blocker
- target organs and their effects on them
- heart
- slowing of heart range and negative inotropic effect
= reduction in CO - Kidney
- Inhibition of Renin release (mostly B1) - brain
- possible central action
Nonselective Beta Blockers
B1 and B2 receptor antagonists
- propranolol
AE: bronchospasms, worsening of diabetes, hyperlipidemia, prolonged hypoglycemia
May also have fatigue, depression, erectile dysfunction
Beta 1 selective agents
Atenolol, metoprolol, bisoprolol
-may enhance Co, contractility and sA node firing.
B1 mediates renin release!!
Inexpensive and have fewer AE
Labetalol, carvedilol
- vasodilitary beta blockersnon-selective B/alpha
primarily beta 3:5
Nebivolol
B1 selective agent
Release of NO
Pindolol, acebutolol
ISA - intrinsic sympathomimetic activity
( beta agonis and antagonist effect)
Prevents dangerous bradycardia at night (due to other beta blockers)
Adverse Side Effects of Beta Blockers
- heart
- Contradicted during acute heart failure
- Intensification of AV block
- Arterial insufficiency
- bradycardia - CNS
- depression
- confusion
- fatigue - Pulmonary
- Dyspnea
- Bronchospasm
Indications for use of Beta blocker in HTN
younger patients (greater adrenergic activity or elevation of plasma renin)
May have less stroke prevention in the elderly
Indications for use of Beta Blocker in Cardiac Disorders
- tachycardia
- Chronic LV dysfunction
- CAD - coronary artery disease
- Hypertrophic subaortic stenosis
Indications of beta blocker in non-cardiac disorders
Vascular (migraine) headache prevention
Essential tremor and performance anxiety
Diltiazem Hydrochloride
Calcium Channel Antagoinst
- used in atrial fibrillation
- decreases HR
- decreases Myocardial contractility
- decreases nodal conduction
- increases peripheral vasodilation
Verapamil Hydrochloride
Calcium channel antagonists
- decreases HR
- decreases Myocardial contractility
(better than other) - decreases nodal conduction
(better than others) - increases peripheral vasodilation
Nifedipine/ Amlodipine
Calcium channel antagonists
- increase/ no change to HR
- decreases/no change to Myocardial contractility
- no effect on nodal conduction
- increases peripheral vasodilation (way better than Diltiazem and verapamil)
Nicardipine hydrochloride
Calcium channel antagonists
- increase/ no change to HR
- no change to Myocardial contractility
- no effect on nodal conduction
- increases peripheral vasodilation (way better than Diltiazem and verapamil)
Renin- Physiological Regulation
- decrease in renal perfusion = renin release from JG cells
- Increase SNS via B1 receptors = increase in renin
- Angiotensin II production and negative feedback = decrease in renin
- Increase distal tubular Na content = increase in renin release
Differences among ACE inhibitor, ARB and Direct Renin inhibitor:
ACE Inhibitor:
- decrease AII and Aldosterone
- Increase plasma renin level
- increase plasma renin activity (PRA)
- increase vasodilitary peptides ( bradykinin)
ARB:
- decrease aldoserone level
- Increase plasma Renin level, PRA, and AII levels
DRI
- decrease PRA
- decrease in AI, AII, Aldosterone
- Increase Plasma renin LEVEL
Potentinal adverse Effects of ACEi, ARB, DRI
- hyperkalemia (aldosterone inhibition)
- Hypotension
- Worsen renal insufficiency ( disproportionate glomerular efferent arterial vasodilation)
- Fetal injury
- ALL INHIBITORS OF RRA ARE CONTRAINDICATED IN PREGNANCY - ACE-I Cough
What drugs will worsen the following situations of HTN:
- Pregnancy
- Depression
- sexual dysfunction
- Asthma
- Gout
- Constipation
- ALL RRA agents
- beta blockers, central inhibitors
- beta blockers, central inhibitors, spironolactone (potassium sparing diuretic)
- Asthma: Beta blocker (non selective)
- Gout - Diuretic
- Verapamil
Captopril, Enanalapril
ACE inhibitors
Inhibit peptdyl dipeptdase – affects RAAS
and Kallikrein-‐kinin system
Toxicity: ARF in pts wi/bilateral renal artery
stenosis; dry cough; angioedema:
Losartan, Valsartan
AT1 inhibitors; no effect on bradykinin
Similar effects to ACE-‐I; less cough and angioedema
