Antihypertensive drugs Flashcards
central sympatholytic drugs
that act directly or indirectly stimulate central presynaptic α2 adrenergic receptors , with inhibitory effect on peripheral sympathetic control.
Sympatholytic with central action
Clonidine
1) stimulates central α2 adrenergic receptors from the bulbous and hypothalamic structures, decreasing peripheral sympathetic tone and blood pressure.
2) acts on non - adrenergic receptors, respectively imidazoline receptors (I1 receptors).
3) It reduces blood flow to the cerebral and splanchnic area, but without decreasing renal blood flow and glomerular filtration,
!!! which recommends the use of clonidine in patients that associate hypertension with renal failure
4) It does not decrease peripheral resistance and does not produce orthostatic hypotension.
Adverse reactions of clonidine
it frequently causes :
1) sedation,
2) drowsiness,
3) constipation,
4) dry mouth due to inhibition of salivary secretion by central mechanism.
5) It is contraindicated in patients who associate depressive psychosis (may reactivate psychosis).
Sympatholytic with central action
Methyldopa
1) a is analogous to DOPA.
2) It penetrates the brain and substitutes DOPA in the
metabolic chain, causing the synthesis of alpha-methylnoradrenaline (false neurotransmitter)
that stimulates central α2-adrenergic receptors, with the inhibition of the peripheral sympathetic activity.
3) It is used in hypertensives with renal failure. It may be associated with furosemide and vasodilators.
4) It is also indicated in hypertension in pregnancy.
Adverse reactions of Methylodopa
1) sedation,
2) drowsiness,
3) depression,
4) nightmares,
5) dizziness.
Sympatholytic with central action
Moxonidine and Rilmenidine
1) lower blood pressure, especially as a result of the action of the imidazoline (I1) receptors in the bulb.
2) Associate weaker central agonist α2 effect.
Ganglioplegics (trimetaphan)
- act by :
- blocking nicotine receptors from sympathetic and parasympathetic vegetative ganglia and
- decrease the blood pressure with pronounced
orthostatic character. - Sensitization of the heart to the action of catecholamines occurs, increasing the risk of myocardial ischemia and arrhythmias
- The sudden paralysis of the sympathetic and parasympathetic vegetative ganglia explains the numerous adverse reactions and the limitation of the clinical use of these drugs
Neurosympatholytics
act at :
- the presynaptic component of peripheral sympathetic synapses,
- decrease the availability of catecholamines in the synaptic cleft and the blood pressure.
- Guanethidine enters
> the presynaptic terminations, by the same transport mechanism that ensures the recovery of noradrenaline,
> stabilizes the presynaptic membrane and produces a “presynaptic block”, preventing the release of noradrenaline from sympathetic endings.
Neurosympatholytics
Adverse reactions of Guanethidine
- produces a marked hypotension, with a pronounced orthostatic character.
- It is reserved for cases of severe hypertension or not responding to other treatment.
Neurosympatholytics
Reserpine
- prevents the recovery of noradrenaline in the storage vesicles
- Remained in the cytoplasm of presynaptic termination, noradrenaline is largely metabolized by the MAO, thus decreasing the availability of the neurotransmitter.
- In the central nervous system, synaptic deposits of dopamine and serotonin also decrease, which explains other effects of reserpine
(sedation-depression, extrapyramidal disorders)
** The hypotensive effect is slow
Adverse reactions of Reserpine
1) sedation,
2) depressive states,
3) nasal congestion,
4) pyrosis,
5) diarrhea,
6) xerostomia,
7) taste changes,
8) pain and / or swelling of the salivary glands, rarely bleeding of the buccal mucosa.
Alpha-adrenergic blockers
Adrenergic α-blockers
produce vasodilation by blocking α1 receptors
Alpha-adrenergic blockers
Non-selective α-adrenergic blockers :
phentolamine and phenoxybenzamine,
are used in the treatment of secondary hypertension in pheochromocytoma.
The combination with β-adrenergic blockers is required to counteract the effects of catecholamines on the heart.
In the treatment of essential hypertension, selective α1-blockers, such as _____ are currently used.
prazosin, doxazosin, terazosin,
Prazosine
1) blocks postsynaptic α1 adrenergic receptors in the vascular smooth muscle without affecting presynaptic alpha2 receptors.
- As a result, presynaptic α2 receptors may be triggered
by norepinephrine released into the synaptic cleft.
2) By blocking the α1 receptors it produces
arterial vasodilation (with decreased peripheral resistance) and venodilation (with decreased
venous return), which explains the usefulness of prazosin and in the treatment of heart failure.
3) Renal circulation is unaffected. It is used in the medium and severe forms of hypertension, generally being associated with a diuretic, possibly with other antihypertensives
Prazosin acts as an antagonist also at the level of
α1 receptors located in the prostate capsule,
improving the symptoms secondary to prostate adenoma.
It is advantageous in hypertensive men who associate benign prostatic hyperplasia
Side effects of Prazosine
1) orthostatic hypotension,
2) headache,
3) nausea,
4) xerostomia,
5) polyarthralgia.
Rarely, it may aggravate the clinical status of hypertensives that associate angina pectoris of effort, which is why in such patients the association with a β blocker is indicated.
Doxazosin
1) is an α1 selective blocker,
2) with a prazosin-like effect and
3) longer duration of action.
It is indicated in the treatment of hypertension and symptomatology of prostate adenoma
Β-adrenergic blockers
1) lower blood pressure in particular by inhibiting renin
(β1-adrenergic) secretion.
2) It associates cardiac depression (with decreased heart rate).
They can be given alone or in combination with a diuretic and or vasodilator. In the case of
association with vasodilators, they have the advantage that they prevent reflex tachycardia
indications , usefulness , recommandations of
Β-adrenergic blockers
- indicated in all forms of hypertension
- They are useful in hypertension associated with
ischemic heart disease and / or arrhythmia. - It is also recommended in young people with
hypertension due to adrenergic hyperactivity
Adverse reactions of Β-adrenergic blockers
are due to decreased sympathetic beta-adrenergic control and consist of:
- worsening heart failure
- bradycardia,
and in the case of non-selective beta-blockers :
- bronchoconstriction and
- aggravation of peripheral ischemia are added.
!! Administration of βblockers to diabetics under hypoglycemic medication (insulin preparations or oral
antidiabetics) requires caution, as they may promote hypoglycemic reactions and mask the symptoms of hypoglycemia
Propranolol
1) a non-selective β-blocker,
2) without intrinsic sympathomimetic activity and
3) with quinidine membrane effect,
4) is the oldest drug in the group and has long been used as an antihypertensive agent.
!! Is contraindicated in patients who associate asthma or peripheral vascular-spastic disorders
Atenolol
1) is a β1 blocker.
2) It is excreted renal.
In patients with renal impairment, dose reduction is required.
Metoprolol
1) a β1 blocker with relative selectivity (equipotent with propranolol as a β1 blocker, but 50-100 times lower than a β2 blocker),
2) is advantageous in hypertensives that
associate asthma, diabetes, peripheral vascular disease.
Bisoprolol
1) a selective β1 compound,
2) metabolized by the liver, with a long half-life and once per day administration.
Nebivolol
1) is a selective β1 blocker that associates vasodialator effect.
2) Vasodilation is the result of increased NO release at the endothelial level.
3) Produces a significant decrease in peripheral vascular resistance.
4) It has a long half-life, it is given once a day.
Carvedilol
1) a blocker of the β1 and α1 adrenergic receptors,
2) is rarely used as an antihypertensive, and remains a leading adrenergic blocker in the treatment of compensated heart failure.
Labetalol
1) blocks β1, β2 and α1 receptors.
2) The decrease in blood pressure occurs by reducing
peripheral vascular resistance, without significant change in heart rate.
3) It is indicated in the treatment of pheochromocytoma and of some hypertensive emergencies.
Direct vasodilators (musculotropes)
1) produce relaxation of the arteriolar smooth muscle by direct mechanism, with decreased peripheral resistance and venous return.
2) Some compounds also produce venodilation.
3) The decrease in peripheral vascular resistance determines compensatory mechanisms mediated by baroreceptors, the sympathetic vegetative system, the
renin-angiotensin-aldosterone system, with hydro-saline retention and reflex-induced tachycardia.
Hydralazine
1) produces decreased diastolic blood pressure through arteriolar vasodilation.
2) Due to the compensatory mechanisms, it is necessarily associated with a sympatholytic (common
β-blocker) and a diuretic.
Side effects of Hydralazine
- headache,
- nasal congestion,
- nausea,
- anorexia,
- xerostomia,
- palpitations.
After prolonged administration, polyneuritis (pyridoxine
treatment) and lupoid syndrome appear
Minoxidil
1) is a highly effective antihypertensive agent with oral administration.
2) It acts by opening the potassium channels in the membrane of smooth vascular muscle cells.
Adverse reactions of Minoxidil
1) can sometimes be severe - tachycardia,
2) hydrosaline retention with oedema,
3) headache.
4) It promotes hair growth, producing hypertrichosis in women.
5) In men this effect may be useful in the treatment of alopecia, using local applications with minoxidil.
Diazoxide
1) is a substance with a structure similar to thiazide diuretics, which produces arteriolar vasodilation but has no diuretic action.
2) In the first half hour, patients may have
orthostatic hypotension, so it is recommended to maintain clinostatism during this period.
3) It is used only in some hypertensive emergencies, injected intravenously quickly.
Sodium nitroprusside
1) acts both by stimulating guanylate-cyclase in the smooth muscle cell of the vascular wall and by releasing nitric oxide.
2) Blood pressure drops rapidly (within 1-10
minutes), but the effect is short-lived.
3) It is given in venous infusion, in hypertensive
emergencies, under medical supervision with blood pressure monitoring.
Calcium channel blockers
1.Calcium channel blockers lower blood pressure due to arterial vasodilation and / or heart depression
2. can be used in hypertensives that associate renal failure, diabetes, asthma.
They may be associated with other categories of antihypertensive drugs. However, phenylalkylamine-β blockers or benzothiazepine-β blockers, however, require caution.
Dihydropyridines (nifedipine, amlodipine, felodipine)
act predominantly in vessels, with consequent decrease in peripheral resistance. In addition, it would also have an antiatherogenic effect, by preventing calcium overload of the arterial wall.
Phenylalkylamines (verapamil)
work mainly on the calcium channels in the myocardial cell membrane.
Benzothiazepines (diltiazem)
have intermediate action between dihydropyridines and phenylalkylamines
Nifedipine
is the first compound in the dihydropyridine category used in therapy. It can now be used in the form of delayed preparation in the treatment of mild or medium hypertension.
Amlodipine
is a dihydropyridine that is commonly used in therapy, as antihypertensive or antianginal
Felodipine, lacidipine, lercanidipine
are new generation long-acting dihydropyridines that are better tolerated.
Nicardipine
is indicated in the treatment of hypertensive emergencies, administered intravenously, initially in slow bolus, then in venous infusion.
Diltiazem
produces vasodilation and cardiac depressant effects; is used as antihypertensive.
Verapamil
1.is indicated especially in patients with hypertension that associate cardiac arrhythmia and / or ischemic heart disease.
2.It is contraindicated in the presence of heart
failure, bradycardia, atrio-ventricular block.
3.The association with β-blockers requires caution
because they associate the same type of adverse reactions.
4.Combination with digoxin may antagonize the positive inotropic effect of digoxin and increase the risk of bradycardia.
5.As an adverse reaction, it frequently causes constipation, headache.
Angiotensin converting enzyme inhibitors (ACEIs)
1.prevent the formation of angiotensin II as
a result of inhibiting the conversion enzyme. 2.Decreasing the amount of angiotensin II causes
dilation of the arterioles, decreasing total peripheral resistance and blood pressure.
3.At the same time, the secretion of aldosterone decreases and the amount of bradykinin increases (the
conversion enzyme metabolizes bradykinin, in which case it is called kininase II).
4.Increasing the amount of bradykinin has both direct and vasodilatory consequences, as well as the
formation of increased amounts of PGE2 and prostacyclin.
ACEIs work on both the
endocrine-type renin-angiotensin system (represented by juxtaglomerular secreted renin and plasma angiotensin), as well as on local renin-angiotensin
systems in the myocardium and other tissues.
As a result, ACEIs have other beneficial effects, useful in the treatment of heart failure, of patients with acute myocardial infarction and diabetic nephropathy (improves low renal function and reduces proteinuria).
The administration of ACEIs in hypertension can be done alone or in combination with other
antihypertensives
Adverse reactions produced by ACEIs are:
- hypotension,
- dry cough (may require stopping conversion enzyme inhibitors);
- bronchospasm,
- nasal obstruction,
- rashes,
- angioneurotic edema (increased risk in patients with a history of angioneurotic edema of other etiology and those in the black race);
- renal failure (in patients with bilateral renal artery stenosis or single kidney),
- hyperkalemia (due to decreased aldosterone secretion and favored by the association of potassium-sparing diuretics).
Captopril
The first ACEI used in therapy (since 1977), has a rapid but short-term effect, which involves administering 2-3 doses per day.
Enalapril
is transformed into an active form (enalaprilat) in the liver, acting as a prodrug.
Absorption is not influenced by the presence of food and the duration of action is longer than in the case of captopril
Currently many other conversion enzyme inhibitors are used – lisinopril, perindopril, quinapril.
Angiotensin receptor antagonists
1.used in medical practice block AT1 receptors, thus
preventing the effects of angiotensin II.
The effects of angiotensin II are achieved by the
specific action of the membrane angiotensin receptors - AT1 and AT2.
The first compound used in medical practice as antihypertensive was losartan, with
antihypertensive effect due to blocking of AT1 receptors. Currently, other antagonists
(blockers) of AT1 receptors - valsartan, telmisartan, candersartan, irbesartan are commonly
used in HTA secretion. These substances are also known as “sartans”.
The action of AT1 receptors is responsible for:
- vasoconstriction,
- aldosterone release,
- inhibition of renin release,
- increased noradrenaline release;
- involvement in angiogenesis,
- influence of vascular permeability,
- production of cardiovascular hypertrophy.
AT2 receptor function is less well known, with data suggesting beneficial cardiovascular effects (antiproliferative effect).
Angiotensin receptor antagonists have all
ACEIs effects.
As they do not inhibit the conversion enzyme (kininase II), they do not produce cough and may be a treatment
alternative in patients who have ACEIs intolerance.
At appropriate doses, they have other indications: treatment of heart failure; performing “kidney protection” in patients with diabetes (albuminuria decreases); acute myocardial infarction, for cardioprotective effect.
In the treatment of high blood pressure, it is possible to resort to the combination of sartans with other antihypertensives, including with a conversion enzyme inhibitor.
Aliskiren
is the first compound of the category of renin antagonists used as antihypertensive.
It binds to the active site of renin (S3bp), producing direct inhibition of plasma renin activity
and blocking the renin-angiotensin-aldosterone system.
Diuretics act as antihypertensives by :
decreasing the volume and implicitly of the cardiac
output, by saline depletion and possibly by direct vasodilating action.
It is used as antihypertensives especially hydrochlorothiazide, indapamide, and in more severe forms furosemide.
Anti-aldosterone diuretics (spironolactone, triamterene) may be associated with these diuretics to potentiate the diuretic effect or to prevent hypokalemia.
Hydrochlorothiazide
is usually given once per daily, in the morning, with breaks of 1-2 days a week, to prevent secondary hyperaldosteronism and hypokalemia.
It is contraindicated in hypertensives that associate diabetes, gout or kidney failure.
Indapamide
is a thiazide diuretic. It produces vasodilation at low doses and associates weak diuretic action that increases with the dose. It is commonly used in the treatment of hypertension. It is not contraindicated in diabetics.
Furosemide
is a loop diuretic. It can be given orally in more severe forms of HTA or if there are contraindications to thiazides. The injection form is used in hypertensive emergencies.
The anti-aldosterone diuretics, represented by spironolactone
have a modest antihypertensive effect, antagonizing the effect of aldosterone, interfering with the K + / Na + exchange, with the re-absorption of potassium (“potassium-sparing diuretics”) and the elimination of sodium and water.
!! They may be associated with thiazide diuretics or loop diuretics.
!! The association with IEC or angiotensin receptor blockers requires caution, due to the risk of hyperkalemia.
