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H g&&sg&&sc  rB  J?Line 9 F 33___PPT10i.(p!(+D=' = @B +" @  0(  7   xQ0e0e?Rectangle 2  Bc kWays of Lowering Blood Pressure  a     x,0e0e?Rectangle 3  Bc Reduce cardiac output (-blockers, Ca2+ channel blockers) Reduce plasma volume (diuretics) Reduce peripheral vascular resistance (vasodilators)@ Z%ckjc   H)?Rectangle 5%2%D<4___PPT9@ T    j$,\A??Picture 4P   F!?Text Box 60  mBP = CO X T PVR    33y___PPT10Y+D=' = @B +"@1 @}(    L?Text Box 4I} THERAPY OF HYPERTENSION$ g  @  F?Text Box 5_ TLD___PPT9& n Non-pharmacological - lifestyle decrease of salt intake and total fat intake. reduction of body weight. restriction of smoking and drinking excessive amounts of alcohol. regular physical activity, relaxation, lack of stress. increased intake of fruit, vegetables." 8 g ggcc   G A   &  33___PPT10i.-%+D=' = @B +"@3 P j(     f k?Rectangle 4( >B. Drug treatment of hypertension The choice of antihypertensive drug will depend on the relevant indications or contra-indications for the individual patient.6 !gc0   V  H?Rectangle 5v3 1. Drugs influencing sympathetic nerves 2. Angiotensin converting enzyme inhibitors (ACEI), blockers of AT1 receptor 3. Calcium-channel blockers 4. Direct vasodilators 5. Diuretics& g       #        33___PPT10i. ^61+D=' = @B +" @9 `$(  $V $ L`?Text Box 4 `@ 0a) b -adrenoreceptor antagonists (beta blockers)B1 !G!,!0    $ H@?Rectangle 5v^ rMechanism of action: decrease myocardial contractility the fall in cardiac output BP - they reduce renin secretion Possible mechanisms include: -adrenoceptors located on sympathetic nerve terminals can promote noradrenaline release, and this is prevented by -receptor antagonists local generation of angiotensin II within vascular tissues is stimulated by 2-agonists. E -A    Z g#cggccc g/ccc"c+ck c" dr  _    $ N`?Rectangle 7 (1. Drugs influencing sympathetic nerves) ) ( 33y___PPT10Y+D=' = @B +"v @: e]p(E(  ( ( F ?Text Box 4'P  o cardio-selective: b1 blockers atenolol, metoprolol b1 blockers with ISA acebutol b1,2 + a1 blockers labetalol, carvedilol cardio non-selective: b1 + b2 blockers nadolol, propranolol, b1 + b2 blockers with ISA pindolol, oxprenolol   g fCKCCCcCCKCCCC c CCCKCKCCCccCCKCKCCCc   C  C  K  C  K  C  C  C $c$$c$x ^  , r    ( N?Rectangle 5Zg b-adrenoreceptor antagonists* C   ( N`?Rectangle 7 (1. Drugs influencing sympathetic nerves) ) ( 33___PPT10i.@P+D=' = @B +"@< ,(  ,v , F ?Text Box 4m Indication of -blockers Hypertension Angina pectoris Cardiac tachyarrhythmias (sotalol) Positive data in HF (carvedilol, metoprolol, bisoprolol) +ve data in postinfarct (carvedilol, metoprolol, timolol) Others (noncardiac indications)  g&cTcc3c cCcc&4    , N?Rectangle 7 (1. Drugs influencing sympathetic nerves) ) ( 33___PPT10i.@P+D=' = @B +"@= 0o(  0 0 F\?Text Box 4  Adverse effects bradycardia atrioventricular blockade congestive heart failure (unstable) asthmatic attacks (in patients with airway disease) CNS adverse effects - sedation, fatigue & sleep alterations.r8 8 g!cc gcgc$gcgc#cgcccc0B  t   0 N]?Rectangle 5 (1. Drugs influencing sympathetic nerves) ) ( 33___PPT10i. 5+D=' = @B +"N@ =54(  4 4 N?Rectangle 4 (1. Drugs influencing sympathetic nerves) ) (  4 F?Text Box 6 !Beta blocker should be avoided in"" "g,!   4 Fr?Text Box 9Tv_PH@___PPT9"@ X Asthma IDDM Peripheral vascular disease Hyperlipidemia 2nd & 3rd degree heart block@Y Xg$g$X   33___PPT10i.5c+D=' = @B +" @   8 (  8 8 N`y?Rectangle 4 (1. Drugs influencing sympathetic nerves) ) (. 8 L ?Text Box 60   b) a -adrenoreceptor antagonistsB! !G!!    8 Ft?Text Box 9, &^Mechanism of action: - vasodilatation (reduce vascular resistence) and decreased BP by antagonizing of tonic action of noradrenaline on 1 receptors (vascular smooth muscle)V8 x2cuck$c:R 6%  8 Hv?Text Box 11"Y  competitive with: a. short-term action: a non-selective(phentolamine) a1 selective (prazosin) b. long-acting a1 antagonists (doxazosin, terazosin)  ffCC CC CCKC CC CK CC@     (    8 J z?Rectangle 12) D/  non-competitive with long-term action, non-selective  (phenoxybenzamin)NK %j  "    33___PPT10i.5c+D=' = @B +"Q@ @8< (  < < Nz?Rectangle 4 (1. Drugs influencing sympathetic nerves) ) (r < L?Text Box 6V Z Indications of  -adrenoreceptor antagonists4. !-g0  T < F|?Text Box 9  f Hypertension especially in pheochromocytoma. Peripheral vascular disease. Medical treatment of BPH.(g8 2gcf   33___PPT10i.5c+D=' = @B +"i@ XP@8(  @ @  ~^0e0e?Rectangle 4Z  Bc Side effects drowsiness, weakness and orthostatic hypotension (first dose  bedtime administration) for the nonselective agents, reflex tachycardia in patients with coronary disease, angina may be precipitated by the tachycardia. oral administration--nausea, vomiting, diarrhoea urinary incontinence priapism, nasal congestion 0 B0  gcgcDcgjcgcccR       /  0            @ N@~?Rectangle 5 (1. Drugs influencing sympathetic nerves) ) ( 33___PPT10i.PGk+D=' = @B +" @   D (  D D L ?Text Box 40n  yc) Centrally acting drugs !    D F?Text Box 5 a2-agonist actionsV( G  y D F ?Text Box 60 y Methyldopa (Central a2 agonist, false transmitter). Clonidine, Moxonidine, Guanabenz, Guanfacine (direct a2-agonist).z( -  G-G            D N@?Rectangle 7 (1. Drugs influencing sympathetic nerves) ) ( D F?Text Box 9P'7X 4 limited use in the treatment of hypertension. methyldopa hypertension during pregnancy methyldopa causes symptoms of drowsiness and fatigue that are intolerable to many adult patients in long-term use they are seldom used to treat essential hypertension clonidine is potent but poorly tolerated (rebound hypertension, if it is discontinued abruptly, is an uncommon but severe problem) (  c c0cgc-cc:  <  33y___PPT10Y+D=' = @B +"@ H(  H H F@?Text Box 8P  2Adverse effects: - drowsiness, fatigue (esp. methyldopa), depression, nightmares (methyldopa - rarely extrapyramidal features)  driving!! - nasal congestion, anticholinergic symptoms (constipation, bradycardia)  clonidine - dry mouth - hepatitis, drug fever (with methyldopa) - sexual dysfunction, salt and water retention - rebound hypertension (rarely hypertensive crisis)( ( f( 4( ggcczccccc"\  H N`?Rectangle 9 (1. 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