Download Free Medical Antihypertensive Drugs PowerPoint Presentation

Antihypertensive Drugs PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Antihypertensive Drugs", to know about the antihypertensive drugs.

Tags : Pharmacology, Antihypertensive Drugs

Published on : Jul 18, 2021 | Views : 3387 | Downloads : 11

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Antihypertensive Drugs Assoc. Prof. Ivan Lambev (www.medpharm-sofia.eu)
Slide 2-

HYPERTENSION is the strongest modi- fiable risk factor for coronary heart disease. It is also responsible for considerable (potentially preventable) disability from stroke, heart and renal failure. Despite this, usually, hypertension continues to be underdiagnosed and undertreated. Many clinical investigations show the relationship between mean blood pressure (BP) and the risk of coronary heart disease (CHD) and stroke (insultus cerebri).
Slide 3-

Most patients with persistent arterial disease have ESSENTIAL HYPERTENSION. But hypertension is occasionally secondary to some distinct disease: Coarctation of aorta Renal artery stenosis Parenchymal or obstructive renal disease Cushing’s syndrome Pheochromocytoma, etc.
Slide 4-

90% 5% 5% Essential hypertension Renal Others
Slide 5-

ppt slide no 5 content not found
Slide 6-

There is changes in perceived norms recently target values for blood pressure. Norm now taken 135/85 mm Hg. For patients over 60 years old today accepted by cardiologists targeted values for blood pressure are 140/90 mm Hg, and in people over 80 years old they are 150/90 mm Hg.
Slide 7-

Cushing’s syndrome is a side effect of glucocorticosteroids (hydrocortisone, betamethasone, etc.) The main symptom is arterial hypertension.
Slide 8-

ARTERIAL BLOOD PRESSURE is determined by cardiac output and peripheral vascular resistance. The kidney plays a key role in its control. Excretion of salt and water controls intravascular volume, which influences the forces of contraction of the heart. Excretion of renin influences vascular tone and electrolyte balance.
Slide 9-

Increased: peripheral vessel resistance, cardiac output, tone of sympathetic nervous system, synthesis of AII, aldosterone, ETs. Inhibited synthesis of NO, kinins, PGE, PGI2. Arterial blood pressure >>> 120/80 mm Hg at rest
Slide 10-

ppt slide no 10 content not found
Slide 11-

ppt slide no 11 content not found
Slide 12-

ppt slide no 12 content not found
Slide 13-

ppt slide no 13 content not found
Slide 14-

Hypertension of white apron
Slide 15-

SHRSP
Slide 16-

 Drugs acting on the RAAS
Slide 17-

ppt slide no 17 content not found
Slide 18-

a) ACE inhibitors Competitive inhibition of ACE reduces generation of AT II and release of aldo- sterone. Inhibition of tissue ACE in the vas- scular wall is more important for the hypo- tensive effect of these drugs than its action on the circulating renin-angiotensin system. Reduced tissue concentrations of AT lead to arterial and venous dilation.
Slide 19-

Angiotensinogen Angiotensin I Angiotensin II Aldosterone release Kininogen Bradykinin Degradation products Renin Kallikrein ACE (kininase II)
Slide 20-

Angiotensin II and ACE inhibitors Captopril Cilazapril Enalapril Fosinopril Lisinopril Perindopril Ramipril Trandolapril
Slide 21-

CAPTOPRIL (prodrug) (prodrug)
Slide 22-

Unwanted effects: Cough: unproductive; may be due to accumulation of kinins in the lung; occurs up to 10–20 % of patients (more common in women!). Postural hypotension (some- times after the first dose) Disturbances of taste, K+ Rashes, angioneurotic edema Teratogenicity (PRC: D) AH, CHD, atherosclerosis, DM, sclerodremal crisis ACE inhibitors – used in:
Slide 23-

Losartan Irbesartan Valsartan b) AT1-blockers (sartans) Oral: in a once daily dosing regimen. Expensive, but with small ARs.
Slide 24-

AT1-antagonists differ from ACE inhibitors in the following ways (by Tripathy, 2003): They do not interfere with degradation of kinins (so no rise in level or potentiation of bradykinin). They block completely AT1-receptors and therefore alternative pathways of AT generation do not have any importance. They result in indirect AT2-receptor activation. ACE inhibitors result in depression of both AT1- and AT2-activation.
Slide 25-

(β1) (β1 & β2 ) Bopindolol Propranolol Oxprenolol (β1 ISA) Pindolol (with β1 ISA) Carvedilol (antioxidant) Labetalol (β & α )  Drugs acting on the SNS a) Beta-blockers Atenolol Acebutolol (β1 ISA) Bisoprolol Celiprolol (β2 ISA) Metoprolol Nebivolol releases NO
Slide 26-

Mechanism of antihypertensive effect Blockade of β1-adrenoceptors in heart reduces heart rate and myocardial contractility. Blockade of renal juxtaglomerular β1- receptors reduces renin secretion. Blockade of presynaptc β2-adrenoceptors inhibits exocytose of NA. Carvedilol and labetalol also block a-receptors and produce vasodilation.
Slide 27-

ppt slide no 27 content not found
Slide 28-

VDCC ROCC Receptor AP Ca2+ Ca2+ Sarcoplasmatic reticulum Cell wall (–) Beta-blockers AP – action potential, NA – noradrenaline VDCC – voltage dependent calcium channels ROCC – receptor operating calcium channels (–)
Slide 29-

Lipophilic β-blockers (e.g. propranolol) are well absorbed from the gut, but undergo extensive first-pass metabolism in the liver, with considerable variability. Hydrophilic β-blockers (e.g. atenolol) are less completely absorbed from the gut and are eliminated unchanged by the kidney. The dose range to maintain effective plasma concentrations is narrower than that of drugs which undergo metabolism and the clinical response is more predictable.
Slide 30-

Adverse reactions of β-blockers Blockade of β1-receptors may cause bradycardia, AV block, heart failure. Blockade of β2-receptors may cause bronchospasm, intermittent claudication (reducing peripheral blood flow) and hypoglycemia. ATP cAMP 3’,5’ AMP AC PDE Beta-blockers (-)
Slide 31-

Most β-blockers raise plasma concentration of triglycerides and lower concentration of antiatherogenic HDL (probably β3-effect ?). Induratio penis plastica (fibrosis …) Sudden withdrawal syndrome: beta-blockers should be stopped gradually. Nebivolol Selective β1-blocker, releases NO (causes vasodialtion) It has 24 h effect. End Effect/Maximum Effect >90%) CNS effects: sleep disturbance, dreams and hallucinations (more common with lipophilic drugs which cross the BBB).
Slide 32-

Atenolol Bisoprolol Metoprolol Nebivolol Propranolol β1/β2-blocking activity β-blockers 15 50 25 293 1,9 S e l e c t i v i t y (55-65/min 24 h) (55-65/min 24 h)
Slide 33-

Blockade of postsynaptic α1-receptors lowers blood pressure by: Lowering tone in arteriolar resistance vessels. Dilating venous capacitance vessels, which reduces venous return and cardiac output. Selective α1-adrenoceptor antagonists spare the presynaptic α2-adrenoceptors and do not produce reflex tachycardia. b) Postsynaptic α1-blockers
Slide 34-

Postsynaptic α1-blockers Doxazosin Prazosin
Slide 35-

Prazosin It has potentially beneficial effect: - an increase in HDL; - a reduction in triglycerides Adverse reactions (AR): - postural hypotension due to venous pooling (this can be troublesome after the first dose) - lethargy, tolerans
Slide 36-

Doxazosin Indications: arterial hypertension and hyperplasia of the prostate gland (men > 45 years old) Selective postsynaptic alpha-1А-blocker: It blocks alpha-1А-receptors into the smooth muscles of the prostate gland, and the prostatic part of the urethra.
Slide 37-

c) α2a-agonists There are several different α2-adrenoceptor subtypes have been identiﬁed: α2a, α2b and etc. α2a-adrenoceptors appear to mediate sedation, analgesia and hypotension while the α2b-adrenoceptor mediates vasoconstriction and hypertension (i.e. postsynaptic α2-adrenoceptors are probably of the α2b subtype).
Slide 38-

Clonidine ( HCl) - xerostomia (dry mouth) - withdrawal phenomenon - sedation - postural hypotension Methyldopa The stimulation of presynaptic α2a-receptors in CNS inhibits NA release, reduces sym- pathetic influence on the vasomotor centre; reduces peripheral arterial and venous tone. (prodrug: α-methyl-NA is an α2a-agonist)
Slide 39-

Clonidine α-methyl-NA (+) Dopegyt® (α-methyl-DOPA) a
Slide 40-

The stimulation of I1-receptors: in CNS reduces sympathetic tone and lowers blood pressure; in kidney inreases secretion of ANP Moxonidine Rilmenidine d) I1 (Imidazoline-1)-agonists (> t1/2: 1 time daily p.o.)
Slide 41-

e) Adrenergic neuron blockers Guanethidine Reserpine – Numerous adverse reactions (out of date) Rauwolfia serpentina
Slide 42-

Adrenergic neuron blockers use the active transport mechanisms for monoamines to accumulate in the adrenergic nerve terminal. Inside the cell they prevent the release of NA from vesicles.
Slide 43-

ppt slide no 43 content not found
Slide 44-

 Calcium antagonists
Slide 45-

VDCC ROCC Receptor AP Ca2+ Ca2+ Sarcoplasmatic reticulum Cell wall NA (–) Calcium antagonists AP – action potential, NA – noradrenaline VDCC – voltage-dependent calcium channels ROCC – receptor operating calcium channels
Slide 46-

ppt slide no 46 content not found
Slide 47-

Calcium antagonists Amlodipine norm frequent dihydropyridine t1/2 31–47 h, 55–91% p.o. bioavailability 5–10 mg/24 h p.o. (once daily) Nifedipine (tachycardia!) – effective in vasospastic angina Diltiazem (in SR dosage forms) Verapamil (Isoptin SR® – tabl. 240 mg) (22% p.o. bioаvailability, first pass effect – extensive liver metabolism; constipation)
Slide 48-

Adverse reactions Arterial dilation: headache, flushing and dizziness, ankle edema (resistant to diuretics) Bradycardia and AV block (verapamil and diltiazem), constipation (verapamil) Verapamil has potentially hazardous additive effects with beta-blockers, reducing the force of myocardial contraction and slowing the heart rate. Tachycardia (nifedipine, nisoldipine).
Slide 49-

Gingivitis haemorrhagica
Slide 50-

Furosemide Torsemide 20-30% Hydrochlorothiazide Chlorthalidone Indapamide 5% 3% Amiloride Triamterene Spironolactone  Diuretics (p.o. in low daily dose) Indapamide Vasodilator It does not influence serum level of Na+, K+, Mg2+ and Ca2+
Slide 51-

ARs of thiazide and thiazide-like diuretics Hypokalemia, salt and water depletion, hyperuricemia, nocturia, glucose intolerance (dose-related) and hyperglycemia, hyperlipidemia (increased LDL and triglycerides), impotence. In small doses thiazide and loop diuretics reduce the intracellular sodium in the smooth muscle of the resistance vessels, which decreases responsiveness to vasopressor substances.
Slide 52-

 Other antihypertensive vasodilators (used in hypertensive emergencies) Sodium nitroprusside (direct NO donor): i.v. infusion Diazoxide: bolus i.v. (ADRs: hyperglycemia) Nifedipine: sublingually Clonidine: sublingually, i.m. Nitrolingual® or Isoket® spray: sublingually
Slide 53-

Nitroprusside is an inorganic nitro- vasodilator with a mechanism of action similar to that of organic nitrates. It is reserved for hypertensive emergencies. It dilates arterioles and veins, reducing both peripheral resistance and venous return. It is given by i.v. infusion and has a duration of effect of less than 5 min. Metabolism to cyanide within red blood cells terminates its effects. ADRs: Confusion, psychosis, metabolic acidosis.
Slide 54-

 Rational antihypertensive combinations ACE inhibitor + thiazide diuretic Sartan + thiazide diuretic Beta-blocker + thiazide diuretic Beta -blocker + amlodipine or felodipine
Slide 55-

Clinical classification A: ACE inhibitors and AT1-blockers B: Beta-blockers C: Calcium antagonists D: Diuretics
Slide 56-

ADJUVANT DRUGS Platelet antiaggregants Antidyslipidemic drugs Anxiolytics, etc. NONPHARMACO- LOGICAL METHODS – avoiding of the risk factors
Slide 57-

BMI > 30: >>> saturated fatty acids >>> salt and >>> sugar >>> alcohol <<< fruits and vegetables Smoking Lipid status Stress 2/3 of the risk Risk factors for CVD Chomocysteine > 15 mmol/l  Diabetes mellitus Metabolic syndrome Sedentary life style Tachycardia
Slide 58-

ppt slide no 58 content not found
Slide 59-

Никотинът е и ензимен индуктор.
Slide 60-

ppt slide no 60 content not found
Slide 61-

ppt slide no 61 content not found
Slide 62-

Rating of cardio- vascular risk