pharma fouda 2_p73-75.pdf

 There is little evidence to suggest superiority of any particular β-blocker, but β- blockers with ISA should be avoided because the reduction in HR and O2 consumption would be minimal.  They are contraindicated in Prinzmetal’s (variant) angina because...

 There is little evidence to suggest superiority of any particular β-blocker, but β- blockers with ISA should be avoided because the reduction in HR and O2 consumption would be minimal.  They are contraindicated in Prinzmetal’s (variant) angina because they block the β2-mediated coronary dilatation leaving the α1 receptors unopposed → ↑ coronary spasm. Mechanism of β-blockers in exertional angina  They ↓ contractility, HR, and systolic BP → ↓ myocardial work and O2 demand.  They ↑ diastolic (coronary) filling time.  Cause redistribution of blood from normal to ischemic (subendocardial) regions  Cytoprotective effect: they produce metabolic switch from myocardial fat utilization to carbohydrates utilization (i.e. improves myocardial metabolism). Combination of BBs and nitrates ↑ their efficiency & ↓ their side effects: β-blockers Nitrates Combination – HR ↓ ↑ (Reflex) ↓ or no effect – Contractility ↓ ↑ (Reflex) ↓ or no effect – Diastolic filling time ↑ ↓ ↑ or no effect – Blood pressure ↓ ↓ ↓↓ Calcium channel blockers (CCBs)  They are considered first-line treatment for Prinzmetal’s (variant) angina.  They are considered second-line alternative after beta-blockers in chronic stable angina in whom beta-blockers are contraindicated.  Short acting dihydropyridines are associated with increased risk of ACS and should be avoided. Long acting dihydropyridines (e.g. amlodipine) and non- dihydropyridines (verapamil and diltiazem) are more preferred.  Amlodipine is the CCB of best choice for symptomatic treatment of angina and/or hypertension in patients with chronic heart failure. █ Newer options for treatment of chronic angina  pFOX inhibitors, potassium channel openers, and ranolazine are examples of new anti-anginal drugs. These drugs alter the balance between myocardial work and O2 supply by novel mechanism(s) of action.  Their efficacy in treatment of angina is controversial; however they are approved for treatment of chronic stable angina in combination with β-blockers, CCBs, and nitrates. 170 pFOX inhibitors (metabolic mod ifiers): Trrimetazidin ne – Theey are teermed pFOX inhi bitors beccause they partially y inhibit fatty acidd oxidatioon in the myocardium m m. – Thiss “metabo olic switch h” from faats to carbbohydrate utilizationn requiress less O2 cconsumptiion. – By inhibition of fatty acid oxid ation, theyy ↓ intra acellular lactic aciidosis leadding to ↓ intracellular Ca2+ & Na+ acccumulation and ion disturbanc d ce, so they y prevent cell necro osis and preserve p conntractile fun nction. – It do oes not afffect HR, blood presssure or corronary bloo od flow. Potass sium cha annel ope eners: Nic corandil – Nico orandil is a new antia anginal dru ug with 2 proposed p mechanism m ms of actio on:  It opens ATP-depen A ndent K+ c channels in the vasccular wall leading too VD of peripheral and coron nary arteriees.  Nitrate-like e activity: it has a n nitrate com nd ↑ cGMP mponent an P like nitra ates but tolerance tot its effeccts is less m marked. – Likee nitrates, it should not n be used d with sild denafil. Ranola azine – It ↓ intracellular Ca2+ in g the late Na+ curreent that facilitates ndirectly byy reducing Ca22+ entry into myocard dial cells. T Na+ and Ca The reducttion in intrracellular N a2+ load reduces cardiiac contrac ctility and w work. – It do oes not afffect HR, blood presssure or corronary bloo od flow. Antiplatelets and a wering drrugs: see pharmaco cholesterol low ology of blo ood. Choice e of antian nginal drug gs in patie ents with another disease: Angina a with…. Most prreferred Least pre eferred Bronch hial asthma a Nitrates,, CCBs Beta-blocckers Heart fa ailure Amlodip pine Beta-blocckers, Vera apamil Hyperte ension Beta-blo ockers, CC CBs Nitrates Diabete es mellituss Nitrates,, Nifedipine e Beta-blocckers, Vera apamil 171  █ MAN NAGEMENT T OF ACUT TE MYOCAR RDIAL INFA ARCTION (AMI) ( Manife estations: persistentt central crushinng chest pain p + ST segment s elevatio on or depression + patholoogical Q wave + raised biochemical mark kers of my yocardial cell dea ath (tropon nin enzymee). All cases must beb hospita alized in a speciialized coronary care e unit. Non n-pharmacologic th herapy: Patientts presentiing within 12 hours of sympto om onset, the treatmment of ch hoice is percutaaneous co oronary in ntervention n (PCI, or coronarry angiopllasty). A balloon cathete er, guided by x-ray immaging, is introduced d into the occluded o aartery to open it. Pha armacolog gic therap py:  Morphine sullfate (5 mg g i.v.): – T To producce analges sia and ↓ stress oof the patient p → ↓ sympa athetic ddischarge and heart work. – Morphine causes ve on → ↓ enodilatatio vvenous retturn and ca ardiac worrk.  Oxyygen: receent evidenc ce suggessts that routtine O2 addministration has do oubtful sign nificance an nd did not reduce mo ortality.  Nitrroglycerin ne and be ers: to eta-blocke limitt the infarc ct size.  Antticoagulan nt drugs: heparin 1 10,000 IU ii.v. then 5000 5 IU/8h h s.c. esppecially whe en the patient is obe ese or if th here is histtory of prevvious MI.  Thrrombolytic c (fibrino olytic) the erapy: stre eptokinase, urokinas se, or t-P PA as earlly as possiible (see blood).  Sed datives: diazepam 5 mg i.v.  Treatment off Complica ations: – C nic shock → dobutam Cardiogen mine i.v.i - Arrhythmia → lido ocaine i.v. 172