CVS - Antihypertinsive , Durtics Flashcards
Explain The molecular mechanism of Hypertension , Ca increase sites , mechanism of increasing Ca+
-in vascular smooth muscles the Ions
K+,mg is mainly intercellular and the Na,Ca is mainly extracellular, in the case of Na/Ca channels opens they enters tge cells and cause depolarization, and Mg/K+ channel opens and they get extracellular, in case of hypertension the mechanism is that Ca open and it enters the cell and UNITE with protein called Clumodulin then this protein will phosphorylate enzyme called myocine kinase light-chain and then actin and myocin fliment unite to each other and causes V.C and
—Ca increase sites :
1-channels opens
2-binding sites
3-Sarcoplasmic reticulum
—mechanism of increase Ca+
1-a1 activate Gq > ip3 ( inositol triphosphat 3 ) > increase Ca > Vc
2-ADH ( Vasopressin) > Activate V1 > ip3 > Ca increase > V.C
3-Ang 2 > Activate > AT1 > ip3 > Increase Ca > VC
4-Enothlein > Activate ET1 > ip3 > increase Ca > VC
Explain hypotension mechanism, and its factors
-in Case of V.D the ions Mg,K+ channel’s opens and that ions extracellular, and becomes intra cellular which cause hyperpolaraztion which is V.D and happens duo to :
1-B2 > increase cAMP > depolarization of myocin light-Chain > VD
2-PGE2,I2 > increase cAMP > depolarization of myocin light chain > VD
3-M3 > Increase synthesis of Nitric oxid NO / EDRF ( endothelial derived relaxtion factor ) > increase cAMP > VD
explain hypertension, Etiology, types , grades , differences between Agency and emergency, hypertension in case of DM,RF
—Etiology:
1-Essential: no reason and also called primary
2-Secondary : renal , pulmonary , Cardiac , ETC
—Types :
1-Systolic hypertension: ex 175/80
2-diastolic hypertension: Ex 120:100
—Grades :
- Norm : S less then 140 / D less then 90
-stage 1 : S 140-160 / D 90-100
-Stage 2 : S 160-180 / D 100-110
-stage 3 : S more then 180 /
D more then 110
—Differences betwen Agncy and emergency
- if there a hypertension without target organ they means agncy and if there is target organ thats mean it’s emergency and its need to be hospitalised
—Hypertension in DM,RF :
its should be mess then 130/80
Classification of hypertension drugs
-First line drugs :
1-B.B
2-CCB
3-ACEI
4-ARA
-2nd line :
1-Alpha 1 blocker
2-a+B blockers
3-Adrenergic neruon blocker > methyldopa
4- Vasodilators
Explain B.Blockers , Drugs , mechanism, uses , Contraindications
-Drugs :
1-propranolol : non selective, lipophilic
2-metoprolol: B1 , lipophilic
3-Atenolol : B1 hydrophilic
4-Bisoprolol : B1
5-Nebivolol : B1 ,No production
6-Carvedilol : a+B blacker , No production
—mechanism: by inhibition of B receptor its lead to , decrease Cop, decrease renin release , blocking b2 in nerve ending lead to decrease NA release , resting of baroreceptor in cardiac which lead to bradycardia , also they have Vasodilation action which increases synthesis of ,PG , NO , also inhibit a1, this effect only happens with 3rd generation only
—uses :
1-hypertension with cardiac problems such as , IHD,HR,Arrhythmia
2-hypertension with pheochromocytoma = Carvedilol
3-young age with hypertension bcs mean that its from stress thats mean renin and B1 can block it
— Contraindications: obstructive pulmonary disease
-NB!its better to use B1 selective unless its the case required specific treatment
Explain CCB , Drug groups , mechanism of action , pharmacological effect , side effect , uses , Contraindications,
—Drug groups :
1-Dihydroperiden : Nifedipine,Amlodipine , nicardipine> vascular selective
2-Benzodiazepines: Diltiazem
3-phinylalklamine : Verapamil > Cardio Selective
—mechanism:
1-it decrease peripheral vascular resistance by blocking of potential-dependent L type Ca+ channel which lead to decrease Ca+ in smooth muscles of arteries and result of decreasing vascular tone
2-its also decrease heart rate and Cop negative ion-tropic and chronotropic effect in case of use Verapamil , Diltiazem
—Pharmacological effect :
1-Smoothie muscles relaxtion
2-Cell necrosis: decrease cell necrosis bcs Ca+ is essential for apoptosis
3-decrease insulin release
4-decrease nuronal firing bcs Ca+ is essintial
5-Platelets: decrease platelets aggression because Ca+ is essential
—Side effect :
1- Bradycardia ; verapamil , Diltiazem
2- Reflex tachy : Nifedipine
3-hypotension
4-Constapiation : duo to RAAS reflex
—Uses :
-Verapamil
1-IHD
2-SVT
3-hypertrophic obstractive cardiomyopathy
-Amlodipine
4-ischemic renal failure
5-hypertension im pregnancy : nifedipine
—Contraindications:
1-CHF
2-bradycardia, AV block
3-in combination with digoxin or B.B because all of them nogative iontropic
4-Wolf parkinson syndrome: which the patient have accessory bundle of kent
Explain ACEi , drug groups , mechanism of Renal hypertension (RAAS) ,mechanism of action, receptors of Ang 2 , pharmacological effect , side effect , uses , Contraindications
—Drug groups :
1-Sulfhydrnal group : Captopril
2-non SH group : Enalapirl,Enalaprilate
—mechanism of Renal hypertension:
-when renal ischemia occurs and RBF , GFR decreased this lead to Acute oliguria that may develop acute tubular necrosis
- As comoplasatory mechanism , renin is released from jaxtaglumular cells as rescue message to stimulate RAAS as its follows :
-Renin > Angitensigen > Angiotensin’s 1 > ACE / kinins > ACE convert Angiotensin to Angiotensin 2 , And kinins metabolis bradykinies .
-Explanation : renin which released from the kidney goes to Angiotisgen which is inactive form and activating it which lead to Angiotensin 1 and with enzyme ACE converted to be Angiotensin 2 , also with ACE there is Another Enzyme called kinins which metabolise bradykinase which is responsible for VD
-Ang 2 : Acts on 2 receptors
1-AT1 : -its cause V.C and thus mentaine Adequate GFR , in another vascular tissue Ang2 act on AT1 casuing systemic V.C , cell hypertrophy, Increase Apoptosis
2-AT2 : V.D
—Mechanism of ACEI : by inhibition of ACE and kinase the affect will be :
1-decrease conversion of Ang1 to Ang2 = decrease vascular tone
2-decrease Aldesteron > decrease Na/water retention = increase K+
3-increase Bradykinin > increase synthesis of PG > decrease vascular tone
—Receptors of Ang2 :
1–AT1 : activating of AT1 : located mostly in efferent and its G-Protein linked receptor when its activated cause V.C duo to :
1-increase intraglumular hydrostatic pressure = Increase GFR
2-Systemic V.C
3-increase Aldesteron release = salt and water retention
4-Increase Vasopressin > V.C
5-increase proapoptotic protein which is lead to Increase apoptosis , so inhibtaion of this enzyme lead to decrease apoptosis and thats useful in IHD
2— AT2 : V.D
—Pharmacological effect :
-CVS :
1-hypotension without reflex tachycardia : duo to resting of baroreceptor
2-direct V.D action in artery and veins which lead to decrease pre/after load
3-increase Cop ( in patient with CHF)
4-decrease cardiac remodeling: duo to decrease apoptosis, and decrease hypertrophy
-side effect :
1-Cough : duo to accumulation of bradykinin
2-Angioedema :
3-protenuria
4-test changes
5-postural hypotension
6-pregnancy tetrognsis
7-skin rush: duo to sh group
8-hyperkalemia
—uses :
1-hypertension duo to RAAS
2-systemic hypertension
3-CHF : bcs its decrease pre/after load , and increase Cop and decrease Cardiac remodelling
4-late stage of MI
—Contraindications:
1-hypotension
2-Severe RF or renal artery stanosis
3-pregnancy : duo to fetal tetroginisis
4-hyperkemia
5-neutrophilina , thrombocytopenia: duo to bonemarrow depression
6-immunological problems
explain ARA , Drugs , mechanism, side effects , Contraindications
—Drugs :
1-Losartan
2-Valsartan
-mechanism: they are selectively antagonist of Ang2 receptor AT1 which lead to :
1-decrease vascular tone
2-decrease aldesteron release = salt and water retention
3-increase renin > angiotensin 2 > AT2 lead to VD
4-have no effect of metabolism of Bradykinin
-Side effect :
1-hypotension
2-hyperkalima
3-hypatotoxcity
-uses :
1-hypertension in patient who used ACEI and casue cough or Angioedema
-Contraindications:
1-renal artery stenosis
2-pregnancy
explain sodium nitroprusside , mechanism , side effect, use’s
-Drug: Sodium nitroprusside Amp
-mechanism: it consist of nitric oxide which increases cGMP which result of dilation of both veins and arteries and decrease pre/after load
-side effect :
1- it consist of cyanid so it can convert to toxic form and accumulation could casue toxicity more often happens with RF,LF and its antidot its Sodium thiosulfate
-uses :
-hypertension crisis
explain the drug that most used in pregnancy hypertension, mechanism
-Drug : methyldopa Tab
-mechanism: alpha methyldopa convert to methyl norepinephrine centrally to decrease the adrenergic out flow of alpha 2 agonist action from CNS leading to decrease total peripheral resistance and systemic Bp
-uses : hypertension in pregnancy
Explain Centrally acting Antihypertensive drug , mechanism, side effect , uses
-drug : Clonidine Amp
-mechanism: its stimulating the presynaptic a2 adrenoreceptor which lead to decrease noradrenaline reales from both central and peripheral sympathetic nerve terminal
-side effect
1-sedation
2-postural hypotension
3-Constipation
-uses : hypertension crisis
explain the classification of diuretics
1-loop durtics
2-thiazides
3-potassium sparing
4-Carbonic anhydrase inhibitors (CAI)
5- osmotic diuretics
explain loop diuretics, drugs , mechanism,pharmacological effect , side effect, uses
—Drugs :
1-Furosemide amp/tab
2-torasemide amp / tab
3-Ethacrynic acid tab
-mechanism: the location of action is in the ascending loop of henle and they block the transports channel Na/K+/Cl- , also increasing synthesis of PGE1,I2 and improve blood supply of kidney which is lead to excrete :
1-Na/water
2-K+/cl-
3-Ca/mg
4- H+
—pharmacological effect
1-powerful duirsis accompind with loos of K+/Ca/mg
2-Vasodilation
3-increase blood supply of kidney duo to increase synthesis of PgE2,I2
4-VD of pulmonary duo to formation of PG increase
-Side effect:
1-hypovolmia
2-hypotension
3-metabolic alkalosis : duo to loss of H+
4-hyperurecimia : duo to increase uric acid reabsorption in PCT as result of hypovilemia
5-ototoxicty : reversible hearing loss duo to disturbance of ion transportation in inner ear , mostly occurs in high doses
6-allergic reaction : dou to SH group except Ethacryinc acid
-uses :
—Chronic :
1-CHF
2-Liver Cirrhosis
3-RF
—emergency:
1-Pulmonary edema , Cardiac Asthma
2-Acute glucoma attack
3-posinig with water sulable toxins
4-hypertensive crisis : Furosemide IV duo to :
-decrease plasma volume
-decrease vascular smooth muscles
-peripheral VD
explain thiazides , Drugs , mechanism, pharmacological effect, side effect , uses
-Drugs :
1-hydrochlorothiazide
2-Clopamide
2-indapamide all tabs
—mechanism: the location of action is the Proximal part of DCT they block
Na/Cl- transport channel and increase Ca reabsorption , and inhibit Carbonic anhydrase enzyme in the PCT , also decrease Na input in smoothie muscles sensitivity to VC
-pharmacological effect :
1-moderate dursis
2-VD
3-decrease production of interocular fluid
4-decrease loos of Ca+
—side effects:
1-hypokalmia
2-hypomagnsimia
3-hyperurecimia ( duo to competition with urates ) ( its ++ uric acid in urine )
4-hyperclacimia
5-hyperglycemia
6-metabolic alkalosis
7-hypotension
—uses :
1-hypertension ( long term treatment )
2-Chronic peripheral edema in :
CHF , liver cirrhosis, miled RF
3-idiopathic hyperclaciuria
explain K+ sparing , Drugs , mechanism, side effect , use’s,
—Drugs :
1-Spironolactone
2-Amiloride
3-Triamterene
—mechanism: drugs have different mechanism :
1-Spironolactone : its comparative antagonist of aldesteron-dependent-sodium-potassium receptor at the distal site of DCT leading to increase Na/water execration and K+ retention
2-Amiloride/Triamterene : they block the entery of Na/H2o At the distal part of DCT and collecting duct which lead to increase Na/water excration and K+ retention
-side effect :
1-hyperkalamia
2-Acidosis: duo to H+ retention
3-gyncomastia
4-menstrual irregularities
5-erectail dysfunction
-uses of spironolactone:
1-primary hyperaldestornsim ( Cohin syndrome )
2-Secondary hyperaldesttonsim
3-CHF
4-Hypertension
5-hypokalimia
