Pharmacological Effects of Cardiovascular Drugs PDF

Pharm macologica al effects CVS S:  They ↓ BP mainly by decreasin T ng peripheral resistannce but no o refl...

Pharm macologica al effects CVS S:  They ↓ BP mainly by decreasin T ng peripheral resistannce but no o reflex t tachycard ia or channges in th he COP ca an occur. This may be due t either (1) resettting of barorecepto to b ors; and/o or (2) ennhanced p parasympaathetic actiivity.  They ↑ CO T OP (only inn presence of CHF)) due to rreduction of both v venous retu urn (preloa ad), and sy ystemic BP P (afterload d).  They ↓ myocardia T m l changes complic cating accute myoocardial infarction (ventricu lar hyperttrophy, and densee collagen n scar) b because they t preve ent myoc cyte cell hypertrophhy and collagen c s synthesis (i.e. preven nt cardiac c remodeliing). Otheer  They ↓ ap T poptosis, ↓ cell hypertrophy, & ↓ tissu ue c collagen synthesiss (i.e. they t reduce d degenerative change es caused by the action o Ang-II on of n AT1 receeptors). peutic use Therap es Sys stemic hyp pertension n: – Hyperrenin nemic hype ertension. – Normoreninemic hyppertension : because th hey are dirrect VDs. Con ngestive heart h failurre (CHF): – T To ↓ afte erload and d preload through reduction of both systemic vascular resistancee, and aldo osterone rrelease (↓ Na and H2O retention n). – T To ↓ myyocardial hypertrop phy and d dilatation (i.e. ( ↓ remo odeling). To prevent LV L hypertrrophy (rem modeling) er acute MI afte M through h: – ↓ arterial BP (↓ myoca ardial strain n). – ↓ myocytee cell hyperrtrophy, ap poptosis, and a collage en synthessis. Diabetic neph hropathy & microalb buminuria a: – T They ↓ re enal chang ges compl icating dia ephropathyy (mesang abetic ne gial cell a apoptosis,, proliferration, aand colla agen syn nthesis), thus re educing m microalbuuminuria (pprovided th hat renal im mpairmentt is not gra ave). 154 Advers se effects:: C : Dry Coug gh (the moost commo on): inhibittion of ACE leads too accumula ation of bradykinin n and PGs, which caause bronchial irritatioon and spaasm. Treatmentt: stop ACE EIs. Cough h will resolv ve after a fe ew days. A : Angioede ema (edem ma of the e face, to ongue and d throat): du ue to accuumulation of bradykinin or duee to immune e reaction. It may be e life threatening. P : Aggravatio on of Proteinuria P a in patients with h significantt renal failu ure. T : anges: tem Taste cha mporary lo oss of tastte (ageusia a and dysge eusia). O : Orthostattic (First dose) d hyppotension:: especially y in sodium depleted (hypovolem mic) patien nts. Prevention n: start by small at b edtime the en increase e graduallyy. P : cy: teratoge Pregnanc enesis (feta al pulmonarry hypoplas sia and rennal dysfunc ction) R : skin Rash h I : Increased erkalemia)) due to ↓ aldosteron d K+ (hype a e release. L : nia (neutro Leukopen openia): esp pecially in patients with w impaireed renal fu unction. N.B. Th he sulfhydryl group (-SH) ( pres ent in cap ptopril may be responnsible parttially for the im mmunologic cal side effects e e.g g. angioe edema, ta aste chan nges, skin n rash, leukop penia. Contra aindication ns Hyp potension: when sys stolic BP iss less than 95 mm Hg g. Sev vere renal failure or bilateral rrenal artery stenosiis (SCr > 3 mg/dl). Why? W – In these conditions, the use off ACEIs is dangerous becausee they ↓ An ng-II → ↓ VC of the efferent arterioles a → ↓ glomerular filtrattion pressuure and ↓ GFR → on of renal failure in b aggravatio both kidne eys. – Dangerouss hyperkalemia may occur. – Dangerouss neutropeenia may o occur. Pre egnancy and a lactattion: theyy may cau use fetal pulmonary p y hypoplas sia and grow wth retardation. Hyp perkalemia a. Neu utropenia,, thrombo a, or seve ocytopenia ere anemia (ACEIs may caus se bone marrrow depre ession). Imm mune prooblems: whether due to autoimmune diseaases or due d to imm munosupprressive dru ugs. 155  Precautions – Initial dose should be small and at bedtime to avoid 1st dose hypotension. – Frequent monitoring of kidney functions (S. creatinine) and potassium levels one week after treatment and then every 3 months. – Avoid use of K+ sparing diuretics to avoid severe hyperkalemia. – Remember all other contraindications… █ Angiotensin II receptor blockers (ARBs) (Losartan- Valsartan- Candesartan- Telmisartan)  They selectively block AT1 receptors and they exert most of the pharmacological effects seen with ACEIs.  They have no effect on bradykinin metabolism.  They have the potential for more complete inhibition of Ang-II action compared with ACE inhibitors because there are non-ACE enzymes (cathepsin and chymase) that can convert Ang-I into Ang-II.  The adverse effects and contraindications are similar to those of ACE inhibitors but cough and angioedema are less common than with ACE inhibitors. ACE inhibitors ARBs Class Angiotensin converting enzyme Angiotensin receptor blocker inhibitor (ACEI) (ARB) Mechanism Inhibition of ACE leading to: ↓ Blocking of AT-1 receptors VC effect of Ang-II leading to ↓ VC effect of Ang-II ↑ VD bradykinins Efficacy in Less effective because other More effective because it blocks inhibition of enzymes rather than ACE can AT-1 receptor, the final station RAAS convert Ang-I into Ang-II responsible for Ang-II effects. Cough and Frequent due to ↑ bradykinins Less frequent (they do not ↑ angioedema bradykinins) █ Direct renin inhibitors: aliskiren  Activation of angiotensinogen into Ang-I by renin is the rate limiting step in formation of RAAS.  Aliskiren is a recently approved drug for treatment of hyperreninemic hypertension. It inhibits renin activity and consequently the RAAS.  The efficacy and side effects of aliskiren are comparable to ACEIs and ARBs. 156