Anti hypertensive Flashcards
name ACE inhibitors
Captopril
Enalopril
Ramipril
Name the ARBs
Losartan
Olmesartan
Telmisartan
Name the direct renin blocker
Aliskiren
Name the CCB’s
Diltiazem
Verapamil
Amlodipine
Nifedipine
Name the diuretics
Thiazides- hydrochlorothiazide
Loop- furosemide
K+ sparing- spironolactone, amiloride
Name the Sympatholytics
Centrally acting: clonidine, a-methyl dopa
B- adrenergic: propranolol, timolol, atenolol, butexolol, metoprolol
B+a: carvedilol, labetalol
a adrenergic blocker: selective- prazosin, terazosin
Non selective- phentolamine
Name the vasodilators
Arteriolar: hydralazine
A+V : sodium nitroprusside
V: nitroglycerin
MOA of ACE inhibitors
1) inhibit generation of angiotensin II
~> no vasoconstriction - ⬇️ PVR - ⬇️ BP
~> no production of aldosterone - ⬇️ retention of Na+ & H2O
~> ⬇️ sympathetic nervous system activity
2) inhibits degradation of Bradykinin (potent vasodilator) by ACE
3) stimulates synthesis of PGs (vasodilators) through bradykinins
PK of ACE inhibitors
Given orally
In hypertensive emergency- enaloprilat given IV
Poorly cross BBB- metabolised in liver- excreted in urine
Captopril- food reduces it’s absorption, hence given 1 hr before food.
Adverse effects + contraindications of ACE inhibitors
CAPTOPRIL
1) cough- dry brassy ~> due to accumulation of bradykinin in lungs ~> drug should be stopped immediately
2) Angioedema- swelling of nose, mouth, lips, throat ~> airway should be protected ~> antihistamines, glucocorticoid, adrenaline given if reqd
3) Proteinuria- rare- in patients with severe kidney disease
4) teratogenic- contraindicated in pregnancy
5) hypotension- 1st dose causes hypotension ( hence low dose should be given) ~> seen in patients who are volume depleted, have CHF, or treated with diuretics
6) rashes & itching
7) loss of taste sensation (dysgeusia)
8) hyperkalemia- patients with renal insufficiency or who are treated with diuretics
9) Acute renal failure- patients with bilateral renal artery stenosis. (contraindicated)
Drug interactions of ACE inhibitors
ACE Inh x thiazides ~> promote loss of Na+ & H2O, ⬆️ anti hypertensive effect
ACE Inh x potassium sparing diuretics ~> severe hyperkalemia
ACE Inh x lithium ~> retard lithium excretion - lithium toxicity
Therapeutic uses of ACE inhibitors
1) Hypertension- used in all grades of HT
- FDC with hydrochlorothiazide
- suited for: HT + coexistant [ DM, asthma, gout, angina, CCF, dyslipidemia]
- C/I : bilateral renal artery stenosis, pregnancy, hyperkalemia
- does not cause electrolyte disturbances, hyperuricemia, sexual dysfunction, alterations in lipid levels.
2) Acute MI- ⬇️ load on heart, ⬇️ O2 consumption so that ischemic myocardium survives longer.
- hence should be started within 24 hrs
3) CHF- prescribed to all patients with impaired left ventricular function
1st line drug- ⬇️ after load, ⬇️ workload on heart
4) diabetic nephropathy- ⬇️ systemic BP & dilates renal efferent arterioles
- hence ⬇️ intraglomerular pressure; Inh angiotensin II mediated mesangial cell growth ~> ⬇️ microalbuminuria
5) scleroderma renal crisis- prevent effects of a angiotensin II in renal artery.
MOA of ARB’s
- 2 angiotensin II receptors [ AT1 & AT2] ~> most angiotensin II effects are mediated by AT1
- ARB’s inhibit binding of angiotensin II to its receptor and block it’s effects
- effects similar to ACE Inh [except they don’t affect bradykinin production]
Adverse effects of ARB’s
Better tolerated than ACE Inh Headache Hypotension Weakness Rashes Nausea Teratogenic effects Hyperkalemia in patients with renal failure or on K+ sparing diuretics
Use of ARB’s
1) Hypertension
2) CCF
3) MI
4) diabetic nephropathy
Indicated in patients who develop cough with ACE Inh
MOA of thiazide diuretics
Thiazides- Inh Na+ - Cl- symport in the DCT Promote Na+ & H2O excretion ⬇️ CO ⬇️ BP on chronic therapy: ⬇️ Na+ conc in the vascular smooth muscle ⬇️ PVR ⬇️ BP
Use of thiazide diuretics
Thiazides- used in mild to moderate HT
- long duration of action
- administered low dose 12.5 to 25 mg/day
Given with K+ sparing diuretics or with ACE Inh
[to counteract loss of K+ and ⬆️ anti HT efficacy]
- well tolerated by elderly patients~> ⬇️ fracture incidence in old ppl due to reduction in Ca 2+ excretion
Use of loop diuretics
Short duration of action
to used routinely - except in presence of renal/ cardiac failure
MOA of B- blockers
B-blockers block B1 receptors on;
Kidney: ⬇️ renin release ~> ⬇️ BP
Heart: ⬇️HR, ⬇️ FOC, ⬇️CO ~> ⬇️BP
CNS: ⬇️ sympathetic outflow ~> ⬇️ BP
B-blockers use & A/E
1) Young hypertensives with ⬆️ renin levels
2) patients with angina, post MI, Migraine, anxiety, tachycardia
3) pregnancy
- May ppt CCF and bronchospasm
- sexual dysfunction & nightmares
- use with caution in diabetics in hypoglycaemic drugs
Sudden stoppage after prolonged therapy can cause withdrawal symptoms
Classify anti hypertensive drugs
1) ACE Inhibitors
2) ARB
3) Direct renin blocker
4) CCB
5) Diuretics - thiazides, loop, K+ saving
6) Sympatholytics- centrally acting, B adrenergic blocker, B+a adrenergic blocker, a adrenergic blocker, ganglion, neuron
7) vasodilator- arterioles, venular, A+V
MOA + PK of centrally acting sympatholytic- clonidine
Stimulates the a-2A receptors in the VMC ->
⬇️ sympathetic outflow from VMC
On heart- ⬇️ HR &CO ~> ⬇️BP
On blood vessels- ⬇️ PVR ~> ⬇️BP
Highly lipid soluble, crosses the BBB, has a short duration of action
Adverse effects of Clonidine
ENT- dryness of mouth and eyes
CNS- depression, sedation
Nausea
Postural hypotension
Sudden stoppage- withdrawal symptoms & rebound HT due to:
- super sensitivity of a-receptors
- precipitous release of large amounts of catecholamine
[ treated with IV nitroprusside or labetalol]
Use of clonidine
1) in hypertension
2) to treat withdrawal symptoms- opioid & alcohol addicts, cessation of smoking
3) pre anaesthetic agent
4) antidiarrhoeal in diabetic neuropathy
5) reduce post menopausal hot flushes
6) prophylaxis of migraine
MOA of a-methyl dopa
a-methyl dopa (prodrug) ➡️ a- methyl dopamine ➡️ a-methyl noradrenaline (false transmitter released during nerve stimulation instead of NA) ➡️
Stimulates a2 receptors in VMC- ⬇️ central sympathetic outflow- ⬇️ HR, PVR - ⬇️ BP
Adverse effects and use if a-methyl dopa
Dryness of mouth, sedation, depression, postural hypotension
Rebound HT on withdrawal (milder)
+ve Coombs test in 1/6 patients
Preferred antiHT in pregnancy
MOA of a-blockers
Non selective blockers- block both a1 & a2 receptors in BV
> vasodilation & fall in BP (a1 blockade)
> ⬆️NA release ( due to a2 blockade- tachycardia prominent)
> not preferred in essential HT- useful in HT in pheochromocytoma, clonidine withdrawal, cheese reaction
Selective blockers- block a1 vascular receptors
> vasodilation and ⬇️ BP
> prazosin causes 1st dose phenomenon- postural hypotension after first dose. ( initial dose given at bed time)
A/E + use of a-blocker
Postural hypotension, tachycardia, palpitation, diarrhoea, nasal stuffiness, impotence
1) In pheochromocytoma- in pre op to control HT and restore blood volume
2) HT emergencies- IV phentolamine ( because of rapid onset of action)
> controls HT crisis intraoperatively, due to clonidine withdrawal, due to cheese reaction
3) essential HT
4) BPH- selective a1 blockers to reduce resistance to urinary flow
5) tissue necrosis- phentolamine
6) male sexual dysfunction- local injection of phentolamine with papaverine
7) others- CCF, PVD
Minoxidil, diazoxide, hydralazine , NTG MOA & A/E
Minoxidil- activates K+ channels- hyper polarises vascular smooth muscle- leads to vasodilation- ⬇️BP
> causes reflex tachycardia & Na+ & water retention ~> hence used with B-blocker and diuretic
> used to promote hair growth in male type baldness
Diazoxide- alt. To Na nitroprusside
Hydralazine- directly acting arteriolar dilator
> > causes reflex tachycardia & Na+ & water retention ~> hence used with B-blocker and diuretic
> headache, hypotension, angina, lupus syndrome
NTG-venodilator used in HT with LVF/MI
Acts rapidly but tolerance develops
Sodium nitroprusside
Rapidly acting with short duration of action
Relaxes A- ⬇️TPR by ⬇️ after load
Relaxes V- ⬇️CO by ⬇️ preload
MOA: RBCs split nitroprusside to NO and cyanide (CN)
NO- causes vasodilation
Very unstable and decomposes on exposure to light, hence should be prepared fresh
DOC for HT crisis & also used to improve CO in CCF
Dose: 1.5 mcg/kg/min i.v. Infusion in dextrose
Nausea, vomiting, anorexia, fatigue, disorientation, toxic psychosis ( accumulation of CN)
CN- is metabolised in the liver to thiocyanate and excreted slowly in urine
HT treatment
Non pharmacological- Weight reduction Sodium restriction, Alcohol restriction, K+ rich diet Exercise Cessation of smoking
Pharmacological- initial treatment- ACE Inh. ARBs, CCBs, thiazides
Therapy started with single agent, if that doesn’t work combination therapy used
Hypertensive crisis
Very high BO- 220/120
With progressive end organ damage
BP should be reduced by 25% within the first 2 hours. And then to 160/100 within 2-6 hours.
Sodium nitroprusside- DOC
alt: fenoldopam, enaloprilat, labetalol, esmolol
Pregnancy: hydralazine
