Final Exam 2nd Semster Q Flashcards
- Antiarrhythmic drugs II, III and IV classes: group members, features of antiarrhythmic action, indications, side effects. Example of drug prescription.
-DF of AP : in the resting state K+ ions is found mainly intracellular while Na+ and Ca+ extracellular making the intracellular is negative
-phases :
Phase 0 : rapid depolarization of the cells duo to rapid influx of Na+
Phase 1 : short period of Redepolazation duo to slow influx of K+
Phase 2 : Plateu delay in repolarization duo to slow influx of Ca
Phase 3 : second period of Rapid repolarization duo to rapid out influx of K+
Phase 4 : the resting state is restored , Na is extracellular , K+ back to intracellular by Na/K+ pump
- Difference between Phase 4 in Atrium and ventricular : is the slop the atrium consist of Slop duo to pre entering of Ca+ to the cells in this phase
—Pathophysiology of Arrhythmia:
-Df : its disturbance in the normal heart rhythm and its results from :
1-Abnormal impulse generation
2-abnormal impulse conduction
—
- Classification of arrhythmia:
1-Bradyarrhythmia AV block : drugs > Atropin , Adrenaline , isoprenaline
2-tackyarrhythmia : consist of 4 classes
—————— Classes ———
1A class
—its increase the APD by inhibition of Na channel
-Drugs :
1-Quinidine tab
2-Disopyramide tab
3-Procainamide tab
—mechanism:
1-they block Na+ channel leading to decrease the Rate of Phase 0 depolarization which lead to increase The APD
2-decrease the exitibality on the atrial side slop which lead to decrease the firing of SA nodes
—pharmacological effect :
1- Arropine like action duo to blocked of muscranic receptor
2-hypotension duo to block of à receptor
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
-side effect :
1-Atropin like action
2-hypotension
3-small doses cause increase AV conduction
4-negative Iontropic effect
- uses :
1-Supraventrecular Arrhythmia
2-ventricular tachyarrhytmia
—NB : the difference between Procainamide and Quinidine is that Procainamide cause SLE like
–
-1B class
—they are decrease the APD
-drugs :
1-Lidocaine Amp ,
2-Mexiletine Caps
3-Phenytoin tabs
—mechanism: it decrease the APD by increasing K+ in the 3rd phase ( repolarization) which llead to decreas APD
–pharmalogical effect :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
—uses :
1-ventricular tachyarrhythmia
2-Acute MI > lidocaine
3-Arrhythmia with over dose of cardiac glycosides > phenytoin
–
Class 1C
—they have no effect of the APD
-Drugs : Propafenone amp ,Ethacyzin tab
-mechanism: by slowing the influx of sodium ions into the cardiac muscles cells causing decrease in :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
-uses :
1-Supraventrecular
2-ventricular Arrhythmia
———————–
— class 2 are B.Blockers
-Drugs :
1-selective : B1> metoprolol ,Atenolol
2-nonselective : Propranolol tabl
-mechanism: they block Sodium, Potassium, Calcium , channel’s which lead to inhibition of phase 4 and depress Autmoticity and prolong Av conduction , alsodecrease HR , :
Automatism↓
Excitability ↓
Conductivity ↓
Contractility ↓
—Side effect :
1-CVS : decrease conductivity, bradycardia , AV block , hypotension
2-Respiratory: bronchispasm
3-GiT : dyspipsia
4- CNS : inly lipophlic drug such as propranolol > depression
-Uses :
1-Supraventrecular
2-And ventrecular tachyarrhythmia
————————
—3rd class
-They are K+ channel blocker
-Drugs :
1- Amiodarone Tab / Amp
2-Sotalol
-mechanism: inhibition of K+ channel in phase 3 which prolongate The Apd also inhibit Na+ and Ca+ , also casue Cornary V.D
-side effect :
1-Bradycardia
2-Arterial hypotension
4-Pulmonary fibrosis
5- photo sensitivity
6-hyperthyroidism
-uses : most type of arrhythmia
-contraindication: Arrhythmia duo to thyrotoxicosis
———————-
-4th class
-They are clacium channel blocker
-Drugs :
1-Verapamil
2-diltiazem
-mechanism:its prolongate the APD through inhibation of Ca+ in phase 2 pleatue ,:
Conductivity ↓
Contractility ↓
Excitability ↓
Automatism:
atria ↓
—Side effect :
1- Decrease conductivity
2-bradycardia
—uses : superventercular tachyarrhythmia
27 Antiarrhythmic agents used in bradyarrhythmia and AV-block of the heart. Example of drug prescription.
-Classification:
1-M Cholingric blocker : Atropin high dose
2-B agonist : Isoprenaline amp
3-a,B agonist: NorEpinephrine
-Pharmacological effect :
1- Increase contractility , conductivity,Automatcity ,COP
-Side effect :
1-Tachycardia
2-Atropine like action
3-Cardiac aresst
4-Tremors
5-Hypokalemia
28 Principles of pharmacotherapy of coronary artery disease. The main groups of antianginal agents. Nitrates: mechanism of action, indications, side effects. Example of drug prescription.
—DF: impaired blood flow through the coronary Artery duo to :
1-Organic Athresclerosis
2-Thrombosis
—Pathophysiology:
-Types of IHD
1-Chronic Stable angaina
1.1 its duo to atherosclerosis and narrowing of the major branch of the heart
1.2 pain induce by effort
2-Acute Coronary Syndrome:
2.1 unstable Angina: its duo to rupture of the plaque
2.2 MI : its next stage of which above and charectrazed by complete occludes of the Epicardial Coronary Artery
3-Prenzmetal Angina ( vasospasmtic ) : its duo to a receptor overactivity , and its happen even in rest
—Pathogenesis:
- its imbalance between oxygen demand and supply of the heart
—————-
–Classification :
1-Nitrates / Nitrates like agent
2-B adrenergic Blockers
3-Calcium channel blocker
4-Other drugs : Ivaberdini tab 0,005
———
—Drugs :
1-Nitroglycerin tab 0.003
2-Isosorbide Dinitrate
3-Isosorbide Mononitrate
4-Molsidomine
— Classification:
1-Short acting
1.1 Nitroglycerin ( Suplingual )
1.2 Isosorbide Dinitrate (Suplingual)
2- Nitrate like Agent: Molsidomine
3-Intermediate Act
3.1 Isosorbide dinitrate ( tab)
4-long acting
4.1 Isosorbide Mononitrate
—Pharmacokinetics:
-Absorption: good
-FPM: 90% While Mononitrate have no FPM
—Mechanism of Action :
-Nitrate release nitrate Oxide (NO) by the effect of Enzyme called Mitacondrial Aldahyed dehydrogenase 2 , NO stimulate Soluble Guanyly Cyclase and cause increase of the second massenger cGMP which is results of Smooth muscles relaxation by stimulating dephosphorlation of myosin light-chain phosphate which lead to :
1-Arterial dilation > decrease Pulmonary vascular resistance which is decreasing post load = decrease myocardial demand of O2
2-venous dilation > decrease venous return > decrease endosystolic volume > decrease pre load = decrease myocardial O2 demand
3-when Endosystolic decrease leads to decrease ventricular wall tension which lead to increase Sub endocardial blood flow = increase myocardial oxygen supply
4-Coronary vessels dilation > increase myocardial oxygen supply
—Additional effect :
1-relaxation of most smooth muscle ~ git , bronchi
2-decrease aggregations
—Side effect :
1-reflex tachycardia
2-Postural hypotension
3-Fascial flushing > duo to venous dilation
4-headache and dizziness
5-Tolerance
—Uses :
1-HR > Nitroglycerin, Isosorbide dinitrate suplingul
2-IHD > isosorbide mononitrate
3-Acute Coronary syndrome , MI > IV nitroglycerin
—Contraindications:
1- mixed it with drug of PhospateDieastrase type 5 such as Sildenefi its potent the action of nitrate , and cause postural hypotension
- Mechanisms of antianginal action of β-adrenergic blockers and calcium channel blockers, indications, side effects. Example of drug prescription.
–B blockers
—Drugs :
1-Propranolol > lipophilic , 1st gen , no selective
2-Bisoprolol > 2gen , selective B1
3-Metoprolol > lipophilic ,2gen , selective B1
—mechanism of action : They block B adrenergic receptor and decrease
cAMP which lead to decrease Ca result in effect on the heart and kidney which lead to :
1-decrease HR
2-decrease contractility
3-Decrease Renin
—side effect :
1-headache drawnness
2-bradycardia , AV block
3-hypotension
—Uses :
1-chronic classic angina
—Contraindications:
1-Vasospastic angina ( Premzemtal )
2-AV block
3-AHF
3-Bronchial asthma
————————————————————–
CCB blocker
—Drugs :
1-Verapamil 1gen
2-Diltiazem 1gen
3-Amlodipine 3 gen
—mechanism:
-They Block potential-dependent L-Type of calcium channel which decrease transmembrane Ca2+ current to heart and arteries which lead to :
1-Decrease myocardial oxygen demand duo to :
1.1 decrease HR ( verapamil )
1.2 decrease Post load
2-increase myocardial oxygen supply duo to :
2.1 Coronary dilation
2.2 increase subendoccardial blood flow
—Phramalogical effect :
1-Antihypertinsive
2-Antiarrhytmic
3-decrease Platelets aggregations
—Side effect :
1-CVS : bradycardia, AV block , reflex tachycardia
2-GIT : dyspepsia
3-CNS: headache
4-Allergic reaction
—uses :
1-Stable angina
2-Vasospastic Angina
3-hypertension
4-tachyarrhythmia
- Calcium channel blockers: classification, pharmacological effects, indications, side effects. Example of drug prescription.
—Drug groups :
1-Dihydroperiden :1st gen Nifedipine, 3rd gen 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
- Hypolipidaemic drugs: classification, mechanisms of action, side effects. Example of statin prescription.
1- HGM-CoA recutase enzyme inhibitor drugs
—Drugs :
1-Atorvastatin tab
2-Rosuvastatin Tab
—mechanism:
they are competitive inhibitor for HGM-CoA enzyme inhibitor which lead to decrease cholesterol synthesis in the liver and increase uptake of LDL
-side effect :
1-hepatic dysfunction : reversible
2-myopathy,myositis
3-GIT upset
4-Cataracts in the eye
-Uses :
1-hypercholystronemia
—Drug interaction :
1-CYP450 inhibitor , which may induce the myopathy and myositis
2- also combined with Fibrates
——
2- The PCSK9 inhibitor drug
—Drug : Alirocumab Amp S.c
—Alirocumab its monoclonal antibody for PCSK9
-mechanism: PCSK9 its protein synthesis by many tissue in the body including the liver and its promotes lysosomal degeneration of LDL receptor in the liver , So inhibiting of this receptor lead to increase LDL receptors
—Side effect : flu like symptoms
-Uses : hypercholestrolenima
——
3-Fibrates
—Drug : Fenofibrate tab
-mechanism: its act on nuclear receptor called PPAR-a proxisome proliferator activated receptor Alpha leading to increase synthesis of lipoprotein lipase which lead to increase catabolism of VLDL and chylomicrons
—Side effect :
1-GIT upset
2-increase formation of Gall stones
3-reversible hepatic dysfunction
4-myopathy
—Uses :
1-hypertriglyceridnemia
2-Combined hyperlipidnima
3-dysbetalipoprotenima
4-mixed hypertriglycerdenima
—–
4-nictonic acid
—Nicotinic Acid tab SR NB! its Vitamin B3
-mechanism: Niacin inhibit lipolysis of triglycerides from the adipose tissue
which is lead to decrease the catty acids that reach. the liver results of decrease synthesis of LDL and VLDL
-side effect :
1- skin flushing and burning sensations
2-hyperglycemia
4-GIT upset
-uses :
1-Hypercholstrolenima
2-hypertriglycerdneima
3-Combined hyperlipidenima
——–
5- Cholesterol Absorption inhibitor drugs
—Drug : Ezetimibe tab
-mechanism: its selective inhibitor of cholesterol absorption and its effect even in absent of diatry fat becs its inhibit Reabsorption of cholesterol that excreted in the bile
-uses : hypercholstrenemia
——
6-Bile acid sequestrants drugs
-Drug : Cholystyramine tab
-mechanism: its bind to bile acid in the intestine and decrease absorption of cholesterol and decrease cholesterol storage in the body
-Side effect :
1-GiT upest
2-Decrease Absorption of the Fat sulobale drugs or Vitamins
—uses :
1-Hypercholestronima
32 Diuretics: classification, comparative characteristics, indications for use, side effects.
Example of drug prescription.
—they are 3 main groups ——
1-loop diuretics
—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
———-
2- thiazides drugs
-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
——————
3-K+ sparing
—Drugs :
1-Spironolactone tab
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
———————–
4- Carbonic anhydrase inhibitor
-drugs :
1-Acetazolamide tab
2-Brinzolamide eye drops
—mechanism: inhibition CAI lead to decrease H+ formation inside the cell , decrease Na/H+ anti-port, increase Na+ and HCO3 in lumen which is lead to increase duress
—mechanism in the eye : its decrease the formation of Aqusomer fluid in the Eye which is lead to decrease IOP
—pharmacological effect:
1-mild duress
2-sever acidosis
3-decrease ICF
4-Decrease IOF
—uses :
1- no druess use anymore duo to acidosis
2-glucoma
3-intercernial hypertension
4-as adjuvant drug for epilepsy
-Contraindications:
1-Liver cirrhosis duo to decrease execration of ammonia which lead to hepatotoxicity
—————————-
NB! tha diffrinses on mechansim , side effect , uses
33 Antihypertensive drugs: the main groups, mechanisms of antihypertensive action, indications for use, side effects. Example of drug prescription.
—ACEi , drug groups —–
—Drug groups :
1-Sulfhydrnal group : Captopril tab
2-non SH group : Enalapirl,Enalaprilate tab
—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
–ARA , Drugs ——-
—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
- Classification of antihypertensive agents for localization of action. Central sympatholytics: mechanisms of action, indications, side effects. Example of drug prescription.
-First line drugs :
1-B.B
2-CCB
3-ACEI
4-ARA
5-diuretics
-2nd line :
1-Alpha 1 blocker
2-a+B blockers
3-Adrenergic neruon blocker > methyldopa
4- Vasodilators
——————————–
-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
—————————————
-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
——————————————-
-drug : Clonidine Amp ( central acting )
-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
- Cardiac glycosides: mechanisms of action, pharmacological effects, comparative
characteristics of drugs, indications. Symptoms of cardiac glycoside intoxication and
treatment principals. Example of drug prescription.
—Df: its progressive clinical syndrome in which either structural or functional abnormalities impair the ability of the heart to meet the metabolic demands of the body
—Classification: they are 2
1-Anatomical:
1.1 Anatomical left-sided : usually duo to systemic hypertension
1.2 Anatomical right-sided : caused by to many things such as pre load , left-sided HF cause Pulmonary Conjation which lead to fail of the right side
1.3 in both sided
2-Pathophysiological :
2.1 systolic : ventricle cant pump the blood through systolic phase which is bcs the muscle are week Ex> ischemic heart disease
2.2 diastolic : duo to hypertrophy the heart cant pump the required amount if the blood in the filing phase
—Clinical manifestation:
decrease Cop leads to following mechanism:
1-sympathetic over activity duo to decreased oxygen to brain leading tachycardia
2-renal ischemia : increase of RAAS ( renin angiotensin aldosterone system) lead to V.C and aldosterone lead to salt and water retention which lead to increase after load and preload and more heart failure
–Groups :
1-Positive Iontropic
- Cardiac glycosides > digoxin
- Debutamine ( for short term only )
- phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors
3-V.D
4-B.Blockers
——-
—– glycosides
—Drugs :
1-Digoxin Tab 0.003
2-Strophanthin K Amp
-Chemical structure: it consists of :
1-Steroid nucleus : lipophilic and essential for activity
2-Lacton ring : hydrophilic and essential for activity
3-Series of sugar : linked to C 3 of steroid and isn’t essential for activity , changing in the glucose would lead to changes in the pharmacokinetics
—molecular mechanism:
its inhibit Na+K+ atapse enzyme , Entering of the sodium to the cell is Passive action so we dont need The
Na+/K+atapes pump so accumulation of the Sodium inside the cell and K+ extracellular, Accumulation of intercellular Sodium leads to :
1-increase the Calcium release from the Sarcoplasmic reticulum
2-Displacement of intercellular Calcium from binding site
3-increases intercellular Sodium prevent Calcium explosions from the cell by inhibition of Na+/Ca+ exchanger
—Autonomic effect :
1-increase Vegal activity > bradycardia
2-decrease sympathetic activity duo to better Oxygenation
—Pharmacological effect :
1-increase Contractility duo to accumulation of Calcium
2-decrease RAAS secretion
3-relief of lung conjation
4-decrease HR duo to vegal increase of vegal tone
5-Normalization of of the Bp
—Uses :
1- chronic HF> digoxin
2- Acute HF > Strophanthin K
3-Arterial fibrillation
– sympotoms of glycosides intoxication:
1-CVs ; sevser bradycardia , AV block
2-CNS : fatugi
3-GIT : anuroxia , vomating , nausea
4-Kindeny : decrease durisis
5-hypokalemia and hypercalcima
–Treamtnet of toxicity :
1-Stop digitalis
2-curratrion of hyopkalimia by giving K+
3-Atropine high dose if there is bradycardia or AV block
4-antiarrhythmic drug
- Non-glycoside inotropic agents: mechanisms of action, indications for use, side effects. Example of drug prescription.
1-Positive Iontropic
- Cardiac glycosides > digoxin
- non glycosides - Debutamine ( for short term only )
- non glycosides - phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors
3-V.D
4-B.Blockers
———————
1–Phosphodieastrase inhibitor drugs in HF ( Bipyradins )
-Drug : Milrinone Amp
-mechanism: they inhibit PDE enzyme type 3 which lead to increase cAMP and cAMp leads to Increase Calcium influx in myocardial cells which results of increase the strength of Contraction
—Adverse effect :
1-Thrombocytopenia
2-increase liver toxicity
-uses :
1-they are used IV only for short term treatment of CHF for patient who digoxin doesn’t affect on them
2-For acute AHF ( Acute Atrium Failure)
—————
2–Calcium Sensitizer
-Drug : Levosimendan Falcon 0,25%-5ml
-mechanism:
1-increase the sensitivity of Cardiomyocytes to Calcium by increasing myofilment Calcium by binding to Cardiac troponin in the calcium dependent manner
2- also its selective of Phosphodiestrase enzyme type 3 inhibitor which lead to Accumulation of cAMP which lead to
1-improve contractility
2-and vascular smooth muscle relaxation
—pharmacological effect :
1-V.D
2- decrease pre load and after load
3-Arrhythmoginc effect
-uses :
1-Acute HF
2-Acute decomposition CHF
——————-
3— Dobutamine and Dopamine Amp 0.1 5ml
-mechansim : the CAMP actevates protein kinase which turn on the phosphoralation of Ca2+ channels leades to increase calcium influx and result of increase the cardiac work
-side effect :
1-tachycardia , hypertantion , cardiac arrethmia
-uses acute HF short term only
- Principles of drug therapy for chronic heart failure. The main groups and drugs, mechanisms of action, side effects.
—Df: its progressive clinical syndrome in which either structural or functional abnormalities impair the ability of the heart to meet the metabolic demands of the body
—Classification: they are 2
1-Anatomical:
1.1 Anatomical left-sided : usually duo to systemic hypertension
1.2 Anatomical right-sided : caused by to many things such as pre load , left-sided HF cause Pulmonary Conjation which lead to fail of the right side
1.3 in both sided
2-Pathophysiological :
2.1 systolic : ventricle cant pump the blood through systolic phase which is bcs the muscle are week Ex> ischemic heart disease
2.2 diastolic : duo to hypertrophy the heart cant pump the required amount if the blood in the filing phase
—Clinical manifestation:
decrease Cop leads to following mechanism:
1-sympathetic over activity duo to decreased oxygen to brain leading tachycardia
2-renal ischemia : increase of RAAS ( renin angiotensin aldosterone system) lead to V.C and aldosterone lead to salt and water retention which lead to increase after load and preload and more heart failure
———————–
-Classification of drugs :
1-Positive Iontropic
- Cardiac glycosides > digoxin
- non glycosides - Debutamine ( for short term only )
- non glycosides - phosphodiestrase inhibitor > Milrinone
2-ACE inhibitors : Captopril
3-V.D : Verapamil
4-B.Blockers : propranolol , metoprolol
- the mechansims already known and all of them lead to :
1- Decrease BP
2- decreas aldesteron which is lead to decrease salt and water retntation and lead to decrease PRe/AFter load and Bp
3-perevent mycordial wall thinkness
4-Decrease cardiac remodling by inhbation of RAAS
-Side effect :
1-Hypotnation
2-Bradycardia
3-renal inufficncy
4-hyperkalemia
5-Dry cough and angioedema with ACEI
- Anticoagulants: classification, mechanisms of action, a comparative characteristic of
anticoagulants of direct and indirect action, indications for use, side effects. Example of
drug prescription.
—Df: Anticoagulant medication thats help to prevent blood clots formation
—Classification:
1-Directly acting
1.1 Heparin
1.2 low molecular heparin ( dalteparin,Enoxaparin)
1.3 syntactic pentasaccraid : Fondaparinux
2-directly acting factor inhibitor:
2.1 Rivaroxaban ( inhibit factor 10)
2.2 Dabigatran ( inhibit factor 2 )
3-Indirectly acting :
3.1 Warfarin tab
————————-
—-Direct acting :
—Drug:Heparin S.c / IV
-Pharmacokinetics:
1.1 Absorption: no because breakdown by HCL
1.2 distributable: dosnt pass BBB/Placenta
—mechanism: its action depends on the presence of Natural cloting inhibitor called ( heparin cofactor : Antithrombine 3) in the plasma small amount of heparin cofactor can activate Antithrombine 3 which lead to inhibition of several clothing factor especially factor 10 and 2
-pharmacological effect :
1- Anticougulant in vivo and vitro
2- Stimulate lipoproteins which decrease TGs in serum
—Adverse effect :
1-bleeding the most common side effect : Anti dot its Protamine sulfate
2-hematoma
3-osteoprosis : prolonged use of heparin inhibit proteins that stimulate osteoblast
—uses :
1-treatment of established thrombosis : to decrease its expand
2-prevention of thrombosis
—Contraindication:
1-MI
—-
-Low mulecular wight heparin
—Drugs :
1-Enoxaparin Amp s.c
2-Dalteparin Amp s.c
—mechanism: same mechanism of heparin but more specific on Anti factor 10
—–
-low molecular wight heparin Direct Acting on factors
1-Factor 10 inhibitor
1.1 Drug : Fondaparinux amp
- synthetic polysaccharides that has the same mechanism of lwmh selective inhibitor of Factor 10 and long acting
1.2 Drug : Rivaroxaban Tab
-Selective factor 10 inhibitor has. the same mechanism of LwMH
2- Direct Inhibitor of Factor 2 ( thrombin)
-drug: Dabigatran Tab
-synthetic compound thats acts as thrombin inhibitor, its can be used as alternative to heparin to treat patient with heparin-indenednt thrombocytopenia
————————
–indirct acting :
—Drug : Warfarin tab
-pharmacokinetics:
1-Absorption: good bioavailability
2-distribution : Can cross BBB
—mechanism: Warfarin inhibit Vit K epoxied reeducates enzyme in the liver leading to inhibition of formation of the active form of Vit K which is lead to decrease synthesis of Vit k-dependent cloting factor ( 2,7,9,10) which is lead to inhibation of carboxlase resulting in decrease modification of factors
—pharmacological effect :
1-Anticougulant in vivo
2- long acting 3-7 days
—Adverse effect :
1-bleeding of major organs : can be antagonis by Vit K
—uses :
1- treatment and prevention of : DVT,post operative thrombosis , Cerebral veouns thrombosis
-Warfarin Polymorphism : Variation in dose requirements is different for everyone, and genetic factors have an effect on dose variation. Polymorphism of vitamin K epoxide reductase complex 1 (VKORC1) gene is identified as the main genetic factor involved in warfarin dosage requirement variations.
–CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation.
- Antiaggregants (antiplatelet drugs): classification, indications for use, side effects. Example of drug prescription.
—Classification:
1-NSAIDS
2-grel
3-phosphodiestreas inhibitor
4-Monoclonal Antibody
——
1-NSAIDs
—Drug : Acetylsalisalic Acid Tab 0.1
-mechanism: its inhibt Cox irrivarsbaly witch lead to decrease THA2 which is responsible for platelet agg
-Pharmacological effect :
1-in low dose : anti agg
2-in high dose : analgasic and antypyratic , anti inflammatory
—side effect :
1-Git ulceration
2-risk of bleeding
3-bronchospasm
—uses :
1-prophylaxis of thrombosis’s
2-to reduce MI recurrent
—————————-
2-Grel
-Drugs :
1-Clopidogrel Tab
2-Prasugrel
3-Ticagrelor
—mechanism: they bind to receptor in the platelets called P2Y12 in site of the chemical mediator ADP should bind to start the aggression , so they bind to this receptor and inhibit ADP from binding and activate of GP2b/3a which is required for platelets to bind to fibrinogen and each other
—Pharmacokinetics:
1-Ticagerlor : 1-3 h and bind irreversibly
2-prasugrel : 2-4 h bind reversible
3-Clopidogrel : 3-5 days bind reversible
—metabolism: they metabolic by CYP450
-Clopidogrel : this drug is pro drug witch mean is that need to metablose to be active , So clopidogrel is metabolize By CYP2C19 , People with polymorphism of this gene lead to reduce clinical responseof Clopidogrel ,
-Drug such as Omeprazole is inhibit the CYP2C19 which is lead to drug drug interaction
—Side effect : bleeding
-uses : prophylaxis of thrombosis
—————————————————
3-Phophodiestrase
-drug : Dipyridamole tab
-mechanism: they are phosphodiesterase inhibitor which is responsible for converting the cAMP to AMP which is important for increasing Ca2 and increase platelets agg
-Pharmacokinetics:
1-good bioavailability
2-high protein bounded
3-VD
-Side effect :
1-headech
2-hypotension especially in IV
-uses :
1-Protection of stroke with. companion of Aspirin
—Contraindications:
1-Unstabil angania duo to VD effect which can increase the ischemia
—————————
4/Monoclonal Antibody
-Drug : Abciximab Amp ivi
-mechanism: they are monoclonal antibody , binde to Gp3/2a and blocks the binding site which is responsible for fibronogen linking and agg will not occur
-pharmacokinetics:
inhibiton of platelets in 30min
-uses :
in combination with heparin and aspirin for percoutnes Cornary intervantion , and cardiac ischemic complications
- Drugs affecting fibrinolysis: classification, mechanisms of action, indications for use, side effects. Example of drug prescription.
—Drugs :
1-Urokinase iV , : its products from kidney
2-Streptokinase IV : its from streptococcal
3-Alteplase IV : tissue plasminogen activator or TPA made by genatic engeneering
—– all pwoder
—explainion of the mechanism: normally when fiber clot is formed plasminogen get in contact with the clot and becomes activated into plasmin By the help do naturally occurring tissue called
( tissue Plasminogen activator T-PAs)
and plasmin causes fibrolysis
—mechanism:these drugs cause Rapid activation of T-PAs to form plasmin , and cause fibrolysis
-side effect :
1-systemic bleeding
2-allergic reaction , fever , hypotension ( streptokinase)
—uses : Acute MI
- Glucocorticoids. Mechanisms of anti-inflammatory, immunosuppressive and anti-allergic action. Indications and contraindications to the prescription of drugs. Example of natural glucocorticoid prescription.
—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0
5-Drug: Betamethasone oint,Amp
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
———–
-michaism of antiinflammatory action , -michism of antiallrrgic , immunusuprrasive mechansim
-Anti inflammtory , anti immunological
-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction ( immeune supprqasive )
-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines (antiinflammatory )
-3 inhibit macrophages activity and stabilize lysosomes membrane ( immune supprasive )
-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability ( antiallargic )
-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs ( anti inflammatory )
—
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
- Glucocorticoids: effects, side effects of prolonged glucocorticoid therapy. Example of
synthetic glucocorticoid prescription.
—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0 ( synthatic )
5-Drug: Betamethasone oint,Amp ( synthatic )
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli ( synthatic )
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
–
-Pharmacological effect :
1-metabolic effect :
1-1 Carbohydrates metabolism: decrease the peripheral glucose utilization which lead to hyperglycemia
1-2 Protein metabolism: increase the proteolysis which lead to decrease muscle mass and then limbs
1-3 Fat metabolism: Increase lipolysis with redistribution of fat which lead to moon face with buffalo hump ( cushing syndrome )
1-4 salt and water retention: which lead to hypoklamia
2- immunological effect :
-Anti inflammtory , anti immunological
2-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction
2-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines
2-3 inhibit macrophages activity and stabilize lysosomes membrane
2-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability
2-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs
3-CVS :
3-1 hypertension: duo to
salt and water retention and increase sensitivity pf BV and heart to circulating catecholamines
3-2 Antishock : duo to hypertensive and CVS effect , and anti inflammatory action
4- haematological effect :
4-1 increase RBCs and neutrophils and decrease lymphocytes and eosinophils
4-2 increase coagulation factors and plasma lipids
5- CNS effect : initial euphoria followed by depression
6- Eye effect : increase IOP
7- effect on bone : decrease bone matrix bcs the bone has proteins and the glucocorticoids are catabolic of protein
8- effect of growth : growth retardation bcs bones and , decreasing the growth hormone
—Adverse effect :
1-immune suppurations; leading to flaring of infection
2-hypertension: duo to SW retention
3-hyperglycaemia
4-peptic ulcer: duo to decrease synthesis of PGs
5-increase IOP which have high risk of glaucoma
6-osteoporosis
7-thrombosis: bcs PLs decrease
8-withdrawal symptoms
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
———————-
example of prolongod therapy in organ transplant to suppraise the immune system
- Non-steroidal anti-inflammatory drugs: classification, mechanisms of action,
pharmacological effects, indications for prescribing medications, side effects and
contraindications. Example of drug prescription.
-inflammation : its protective response to cell injury to eliminate the harmful agents by remove the damaged tissue and generate new one
-Dynamics of inflammation :
1- tissue injury
2-hormonal response : by V.d and increase the preamblity , Exudation
3-Cellular Response ( proliferation) : migration to inflammatory site , phagocytosis, tissue reparation
— synthisis of ecosanides :
-Starting from phospholipids (PL) transformed Archadonic Acids (AA) by Phospholipase (PL2) give Us steroid anti inflammatory drugs , then The Archdonic Acid ( AA ) transformed to Protsglandins (PGs) by Cox enzyme so Cox enzyme give us NSAID drugs , in the same time AA transformed by another substance which is Lipooxgnase (Lox ) and give us Leukotins drugs
—Eicosanoids: they are fatty acids derivatives
—Synthesis of Eicosanoids:
its start from phospholipids (PL) transformed to Arachonic Acid (AA) by Phospholapes A2 (PL2) then it have 2 pathway
1-with help of cyclooxgynes (cox) generate :
1-1 Prostaglandins (PGs)
1-2 Thromboxan A2 (TXA2)
2-with help of Lipooxgnase (Lox) generate:
2-1 Liukutmins (LTs)
—types : we have 3 types according to the synthesis :
1-PGs 2-TXA2 3-LTs
— receptor of Cyclooxgnease : first we should know that the Cox only effect the PGs and TXA2 and by that we have 2 types of Cox
—types and features of cyclooxegnes
— types of Cox and its effect :
1- Cox1 :
1-1: expressed in most normal tissue
1-2 physiological function :
gastric protection (pge2) , renal blood flow ( pge2) , platelets agg (TXA2)
1-3 pathological function: non
2– Cox2 :
2-1 expressed in the pathological condition: such as inflammation, carcinogenic
2-2 physiological function:
V.d , Anti agg
2-3 pathological function:
inflammation, fever , pain
———–
-Classification :
—non selective
- prototype Acetylsalicylic Acid
1- drug : Diclofenac Tab and Amp
> its less gastric irritation but more nephrotoxic / wildly used for rheumatoid pain
2- drug : Ibuprofen tab or oint 5%-30.0
> its more safe on children but study showed that women under 30 who used it have relatively hypertension from this drug
3- Drug : Indomethacin tab , Oint , Supp , eyedrops
> its the most potent Cox inhibitor but relatively more nephrotoxic
> the most useful for indomethacin is for ductus arterioles
—— Cox2 inhibitors
- they are 2 drugs
-1- Celecoxib Caps
-2- Meloxicam tab or amp
- mechanism: they inhibit Cox 2 enzyme reversibly
- pharmacological effect : Antipyretic, analgesic, Anti inflammatory
- side effect :
1- gastric irritation less frequent
2- renal side effect : more frequent
3- thrombotic complications : increase duo to increasing the platelets agg
— non NSAID : Paracetamol tab
— the prototype —-
—Drug : Acetylsalicylic Acid Tab 0,05
— Pharmacokinetics:
1- Absorption: is good bcs the drug is Acidic and the stomch HCL is acidic also
2-elimination : its dual root of elimination according to the dose
—mechanism of Action :
Aspirin is non-selective and irreversible Cox enzyme inhibitor leading to inhibit both of PGs and TXA2
NB! the only different between the aspirin and its derivatives its they are reversible and Aspirin is not
—Pharmacological effect and mechanism of each:
1-Analgesic Action : mechanism
1-1 prephrally effect : decrease the synthesis of PGs in prephral tissue
1-2 centrally : decrease the synthesis of PGs in subcortical sites ( hypothalmus and thalamus )
2-Antipyretic: : its not hypothermic but it decreases the elevated temperature Ex:39 to 37
-mechanism:
2-1 decrease the synthesis of PGE2 in hypothalamus
2-2 decrease the hypothalamic response to interleukin
2-3 Coutenous V.D which increase the sweating
3- Anti inflammatory effect :mechanism > by inhibition of Cox enzyme 1 and 2 its decrease the synthesis of PGs and TXa and possible other inflammatory substances
3-1 decrease the inflammatory cell division
3-2 decrease the capillary preamability
3-3 decrease the Hyaluronuides enzyme
3-4 stabilise lysosomes membrane of inflammatory cells
— Side effects :
1- respiratory system:
1-1low toxic dose : produce metabolic acidosis
1-2high toxic dose : produce acidly together with inhibition of R.c leads to death from sever acidosis
1-3increase risk of asthma
2- GIT effect : produce 2 types of gastric ulcer
2-1 acute gastric ulcer : ion trap of aspirin in case of empty stomach
2-2 chronic gastric ulcer : when ingestion of small doses for several years
3- hepatic effect : produce 2 types of hepatic injury
3-1 mild haptic injury : ita dose dependent and asympathomitc there may be increase of serum which is (SGOT and SGPT )
3-2 sever hepatic injury: children under 16 shouldn’t use aspirin bcs its related to Ray syndrome which is liver failure and Encephalopathy
4- hematological effect : by inhibition of Cox its inhibit the platelets agg irreversibly which lead to risk of bleeding
5- kidney: NSAIDs prevent synthesis of PGE2 which responsible for sodium which lead to salt and water retention and Edema
—- Therapeutic Use :
1- As analgesic: for mild or moderate pain
2- As Anti inflammatory
3- Antipyretic
— Contra indication :
1- GIT disorders : such as Peptic ulcer or gastritis
2-hematological disorders: hemophilia
3- Chronic renal disorders: may aggregate the renal failure
4- Gout : small dose may inhibit the uric acid Execration
5-before surgery: risk of uncontrollable bleeding
6-children under 16 : ray syndrome
–Drug drug intraction :
1- Aspirin Antagonist the Urine execration so i. patient with Gout disease which need to execrate the urine and use drug Probenecid they anatagoinse each other
2-Aspirin can replace the Anticoagulant drugs such as Heparin
3-Aspirin Antagonize Anti-acids and decrease the Aspirin Absorption in stomch
———————-
–Paracetamoli tab
—Drug : Paracetamol tab 0.5
—Pharmacokinetics:
1- Absorption: Complete
2-Distribution : goes to all body tissue
3-Metabolism: in liver by
3-1 glucuronic acid 60%
3-2 Sulfate 35%
3-3 hydroxolation by CYP450 , and form toxic form NABQ N-Acetyl-P-Bezoqinon ( can cause liver damage )
— mechanism: has less effect on Cox in peripheral tissue duo peripheral inactivation , Study showed its work centrally on Cox3
—Pharmacological effect :
1- Analgesic
2-Antipyretic
—Side effect :
- Forming Toxic form NABQ
N-Acetyl-P-Benzoqenon which bind to cellular proteins Around the central vein in the hepatocytes and cause > hepatocellular necrosis
—Therapeutic use :
1-Analagisc
2-Antipyretic
- first of all the paracetamol is is very safe and its the first line for children and women who’s in pregnancy
—Antidote: Sulfhydryl > N-AcetylCysteine which contains sulfhdryl form glotatheion to wash the toxic form which is N-Acetyl-P-Benzoqinon
57 Immunosuppressive drugs: classification, mechanisms of action, pharmacological effects,
indications, side effects.
Nb! we can use glycocoticoids or we can use anticancer agents which has immunosepprasive effect such as cyclophosphamide
—————-anticancer agents ————————————
— —Drug groups :
1-Nitrogen mustard : Cyclophosphamide tab/Amp
2-Nitrosoureas : Carmustine Amp
—Mechanism: produce highly reactive intermediates which transfer Alkyl group to cellular micro molecules , At the Position 7th of guinin forming covalent bond which lead to DNA cross linking > resulting of inhibition of mitosis or even apoptosis
—Pharmacokinetics: Cyclophosphamide most alkylting agent used and its pro-drug which it’s required biotransformation in the liver by CYP450 to become active form
-Specific side effect :
1-Hemorrghic cystitis : caused by the metabolite called acrolein and can be prevented by increasing fluid intake or sulfhydrl donor such as
N-Acetlycysteine which is washing the bladder from this toxic form
—uses :
1-AntiCancer drug in most types of cancer
2-As immunosuppressants: such as RA,SLE duo to cross linking in T-cells which is in most cases its the reason of Autoimmune disease
———glycocotricoids ———————
—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug: Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0 ( synthatic )
5-Drug: Betamethasone oint,Amp ( synthatic )
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli ( synthatic )
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
–
-Pharmacological effect :
1-metabolic effect :
1-1 Carbohydrates metabolism: decrease the peripheral glucose utilization which lead to hyperglycemia
1-2 Protein metabolism: increase the proteolysis which lead to decrease muscle mass and then limbs
1-3 Fat metabolism: Increase lipolysis with redistribution of fat which lead to moon face with buffalo hump ( cushing syndrome )
1-4 salt and water retention: which lead to hypoklamia
2- immunological effect :
-Anti inflammtory , anti immunological
2-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction
2-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines
2-3 inhibit macrophages activity and stabilize lysosomes membrane
2-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability
2-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs
3-CVS :
3-1 hypertension: duo to
salt and water retention and increase sensitivity pf BV and heart to circulating catecholamines
3-2 Antishock : duo to hypertensive and CVS effect , and anti inflammatory action
4- haematological effect :
4-1 increase RBCs and neutrophils and decrease lymphocytes and eosinophils
4-2 increase coagulation factors and plasma lipids
5- CNS effect : initial euphoria followed by depression
6- Eye effect : increase IOP
7- effect on bone : decrease bone matrix bcs the bone has proteins and the glucocorticoids are catabolic of protein
8- effect of growth : growth retardation bcs bones and , decreasing the growth hormone
—Adverse effect :
1-immune suppurations; leading to flaring of infection
2-hypertension: duo to SW retention
3-hyperglycaemia
4-peptic ulcer: duo to decrease synthesis of PGs
5-increase IOP which have high risk of glaucoma
6-osteoporosis
7-thrombosis: bcs PLs decrease
8-withdrawal symptoms
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
———————-
example of prolongod therapy in organ transplant to suppraise the immune system
58 Antiallergic agents: classification, mechanisms, pharmacological effects, indications, side effects. Example of antihistaminic drug prescription.
-Histamine formed from amino acid histidine by action of histadine decarboxylase enzyme and stored in the mast cell
-Receptors : there are 4 receptors:
-H1,H2,H3,H4
-Physiological Antagonist of Histamine is : Adrenaline its revert all the actions of Histamine
-Drugs :
1-H1 : Diphenhydramine tab 1gen,Loratadine 2gen
2-H2:Cimetidine , Ranitidine
-H3 and H4 : no clinical use
-Anti-Allirgic drugs are drugs that selctevly inhibit the H1 receptor leading to decreased the action of allergy and its symptoms and they are classified as 2 generation :
-The 2nd generation is more :
1-Selectivky H1 blockers
2-More potent
-Pharmalogical effect :
1-Relive of itching
2-Decrease capillary permeability
3-Decrease bronchial construction
4-Antiemetic only in 1Gen for motion sickness
5-Blocks a receptor only in 1gen
-Side effect :
1-first Gen :
-Sadetion , atropine like action , orthostatic hypotantion
2-2nd gen : they are metabolised by the CYP450 so there is a chance of drug drug intraction and Prolonged QT interval
- Thyroid and antithyroid drugs: classification, mechanisms, pharmacological effects, indications, side effects. Prescribe tiamazole
—synthesis of thyroid glands :
start with activating Uptake of iodide, then oxidation with peroxides enzyme and indentation of tyrosine of theyroglobin to form MIT and DIT
then condensation of MIT and DIT Nd formation of T3 and T4 , then proteolysis of thyroglobulin, then secretion of T3 and T4 into blood stream
—NB! the secretion of T4 and T3 stimulate by TSH , most of T3 is drived from peripheral dioidenation of T4 in the peripheral tissue
-B blockers and corticoids inhibit the peripheral conversation of T4 to T3
—they are used to treat hypothyroidism
—Drugs group :
1-Levothyroxine (T4 )
2-Liothyronine (T3)
all tabs
—hypothyroidism: its clinical syndrome results from high levels of thyroid hormones
-clinical types :
1-Graves disease: its an autoimmune disease in which there abnormal Antibodies > activating TSH receptor in the thyroid gland which lead to enlargement or the gland and softness
2-toxic multinudular goiter : the treatment is usually surgical
—management:
1-graves disease: usually medication
2-multiple nodular goiter : surgical
—Drug : Thiamazole tab 0,005
-mechanism of action: they inhibit the oxidation of Iodides by inhibition of peroxides enzyme
-side effect :
1-agranulocytosis, bone marrow depression duo to formation of antibody that against WBCs
2-hypothyroidism with increased the size of vesicularty of the gland
3-hepatotoxic
4-hypersensitive reaction
–uses : thyrotoxic
- Insulins, insulin analog and oral hypoglycemic drugs: mechanisms, pharmacological effects,
indications, side effects. Prescribe regular insulin or insulin analog.
—types of insulin:
1- traditional ( animal ) : prepared from animal such as pork and beef , animal insulin may contain animal proteins that could cause allergy and its more antigenic
2-human insulin : its identical to human insulin and its prepared by recombinant DNA technology , its less antigenic and rare development of insulin resistance
—insulin secretion: glucose enters B cells which lead to increase the ATP closure of ATP-dependent k channel which lead to opening of voltage gated C+2 channel which increase the calcium influx and insulin release
—insulin receptor : A tyrosine kinase receptor consist of 2 extracellular (a) and 2 subunits of Beta
—mechanism : binding of insulin to the alpha subunit cause activation of tyrosine kinase enzyme which triggers a series of intercellular effects lead to increase the number of glucose transporters ( GLUT4 ) in the cell membrane and increase the transporter of glucose to cell which lead to»_space;>
1-increase glucose transporter in insulin-dependent tissue in Sk muscles and fat tissue
2-stimulation of glycolysis : break down the glucose
3-stimulation of glycogen synthesis: glycogen is the stored form of glucose
4-inhibition of glaconeogensis in the liver : gluconeoginsis is process in the liver which is making glucose from breaking down of lipids or proteins
5-stimulate pintos phosphate pathway ( PPP ) : its pathway generally regulate the body cell tissue , in glucose its metabolize 30% of glucose by this pathway
6- increase the protein synthesis: by activating of mechneray increase EIFs
7-stimulation of Fat synthesis : which is gone decrease the glucose
8-inhibition of lipolysis
–insulin analogs :
regular insulin
-group : short acting
-onset : 0-30 min
-duration : 5-6 h
its the safest insulin in emergency for example used in hyperglycemic coma I.V
2- insulin Aspart
-group : short acting
-onset : 5-10 min
-duration : 3 h
its insulin analog , created by replacement of proline to aspart and the result its fast acting and short duration insulin’s bcs its monomer
3- insulin isophane
-group : intermediate acting
-onset : 1-3 hour
-duration : 12-24 h
its created by replacement of the zinc with protein for the fishes called protamine and its positive charge and bind with insulin molecules ionic bond which lead to take the body long time time to break this bond , and its hexomor
4-insulin glargine
-group : long acting
-onset : 1-3 h
-duration : 12-24 h
its created by adding 2 more molecules of argin to the insulin which made the insulin 53 amino acid instead of 51 which lead to longer duration
—therapeutic uses :
1-T1DM
2-T2DM : in some cases
2.1 after fail of oral drugs
2.2 if the patient got stress conditions such as surgery, infection, pregnancy
3-hyperglycemia coma
4-hyperkalemia : bca insulin and glucose can shift the potassium from blood to tissue
—adverse effect :
systemic >
1-hypoglycemia: its most common
2-hypoklamia
3-hypersensitive reaction
4-insulin resistance : duo to accumulation of carbohydrates, formation of antibody against insulin , decrease sensitivity
locally >
1-local allergy : maybe bcs the animal insulin
2-lipids dystrophy
3-local infection
———-
-oral insulin :
—-oral drugs :
1-family of Sulfonyurea
-drug: Glibenclamide tab 0,007 ( stimulate insulin secretion)
-mechanism of action : it has 2 type of mechanism>
1.1 pancreatic: binding to the SUR1 receptor on B cells and blocked of ATP-dependent K+ channel which lead to depolarization bcs Ca2+ and increase the insulin secretion
1.2 Extrapancreatic : they increase the insulin receptor sensitivity
-side effect :
1-hypoglycemia
2-increase apitite and weight gain
3-allergic recation
4- renal failure > contraindications
-uses : T2DM
-———————————
2- family of megletunds
-drug: Repaglinide Tab 0,0005 ( stimulate insulin section)
-mechanism of action :the has the same mechanism of sulfynurea
-uses : T2DM used for patient with allergies from sulf or has renal failure
-———————————
3- family of Bigunaides
-drug: metformin tab 0,5
-mechanism of action : Stimulate of AMP-dependent protein kinase of hepatocytes which lead to inhibition of gluconeognesis in the liver , and increase the insulin receptor sensitivity
-pharmacological effect :
no risk of hypoglycemia
-side effect :
1-nausea
2-dihrria
3-lactic acidosis: duo to increase of Anarobic glycolysis
-uses : T2DM , wight loss
-———————————
4- family of Thiazolidinis
-drug: Rosiglitazone tab 0,5(insulin sensteiser)
-mechanism of action : its act on nuclear gene called Perixisom-prolifratir-activated-receptor-gamma ( PPAR-y) bind to this gene in liver and adipose tissue , and increase insulin resistance
-pharmacological effect :
they have slow onset because the mechanism involves gene regulation
-side effect :
1-heptoroxic
2-wight gain
-uses : to improve insulin resistance in T2DM
———————————-
5- family of incretin ( glucagon like peptide 1 )
GLP-1
-drug: Exenatide Amp
-mechanism of action : they increase the insulin secretion by binding to B cells and forcing it to secrete it , and decrease the glucagon , and slow the gastric emptying and decrease apitite
-side effect :
1- nausea 2-vomiting 3-pencreatits
-uses : in T2DM and should be giving before eating by 60 min
————————————
6- family of Dipeptidly peptdens 4 inhibitor ( Dpp-4)
-drug:Saxagliptin tab 0,0025
-mechanism of action : they inhibt the DPP-4 enzyme which is responsible for proteolysis of incretin so its decrease the GLP-1 may improve B-cells function and decrease the glucagon secretion
-side effect :
1- nausea 2- headache
-uses : for T2DM usually combined with metformin
———————————
7- family of sodium-glucose cotransporter 2 inhibitor ( SGLT-2 )
-drug: Dapagliflozin tab 0,005
-mechanism of action : increase the urine glucose and sodium secretion
-pharmacological effect :
1- decrease Bp
2-body wight loss
-side effect :
1-polyuria
2-hypotension
3-hyperkalimia
-uses : in T2DM in case of the patient has renal or haptic failure and cant take metformin
- Bronchodilators: classification, mechanisms of action, pharmacological effects, indications, side effects. Example of drug prescription
— Drugs : B2
1- short acting
1.1Salbutamol tab, aears
1.2 Fenoterol
2- long acting :
2.1 Formoterol Caps
2.2 Salmeterol Aers
— mechanism: by activating the B2 receptor it will increase the CAMP which lead to broncho dilation , and suppress of inflammatory mast cells , mediators secretion and reducing of Ach reales from Nerve Ending
—uses : Quick relief , long term controlling of BA in combaination with Glucocorticoids
-side effect :
1- tolerance
2-tremors
3-hypoglycemia
—
-muscarnic blocker such as :
Atropin and ipratropium bromide
————————————————–
-Drugs : Methylxanthines
1-Theophylline Tab
2-Aminophylline Amp
-mechanism:
1- Adenosine ( A1) receptor: these drugs blocks A1 receptor which lead ti broncho dilation , CNS stimulate , decrease mediator’s that secreted by Mast cells , Increase AV conductivity,
2- they inhibit Phosphodiesterase PDE3 and PDE4 which lead to accumulation of CAMP leading to :
1-B.D
2- increase cardiac conductivity, relaxation of most smooth muscle
-pharmocokintics :
1- absorption : full absorption 90-100%
2-metabolism: in the liver Cyp450 ~ CYP1A2 and metabolite to Cafien
3- cleared by smoking bcs its microsomal inducer
4- decrease cleared by microsomal inhibitor ~ Erythromycin
-side effect : nausea, vomiting , dyspepsia , durisis stimulation
-uses : Chronic BA theophylline
Acute BA aminophylline Amp
——————————————————-
- Drugs : glucocorticoids
- there is two types
1-local effect drugs :
1.1 Beclomethasone
1.2 budesonide
1.3 Fluticasone all aresol
2-systematic effect :
2.1 Prednisolone Tab , Amp
—mechanism: bind to cell surface receptors to the cytoplasm receptor carrier then transferred to nucleus where it interacts with DNA then transcription which results of RNA which lead to decreese the synthisis of Pgs and other inflammatory mediators
—systemic Pharmacological effect : mentioned in crticoids
- local pharmacological effect :
1-reducing the inflammation and hyper reactivity of bronchi
2-reducing frequency and severity of BA
—uses :
-local drugs : BA inflammatory
-systematic drugs : Sever asthma ~ asthmatic status IV
———————————————————
- Drugs used to control bronchial asthma: mechanisms, pharmacological effects, indications, side effects. Example of drug prescription.
- Drugs : glucocorticoids
- there is two types
1-local effect drugs :
1.1 Beclomethasone
1.2 budesonide
1.3 Fluticasone all aresol
2-systematic effect :
2.1 Prednisolone Tab , Amp
—mechanism: bind to cell surface receptors to the cytoplasm receptor carrier then transferred to nucleus where it interacts with DNA then transcription which results of RNA which lead to decreese the synthisis of Pgs and other inflammatory mediators
—systemic Pharmacological effect : mentioned in crticoids - local pharmacological effect :
1-reducing the inflammation and hyper reactivity of bronchi
2-reducing frequency and severity of BA
—uses :
-local drugs : BA inflammatory
-systematic drugs : Sever asthma ~ asthmatic status IV
——————————————————— - prophylactic drugs ( the main for the quasiton )
we have 3 families of these drugs
1-Luktraines
2-Mast cells stabilizer
3-MABs
———
1- Leukoutraines inhibitors
-Drugs :
1-Zafirlukast tab
2-Montelukast tab
-mechanism: they inhibit LTD4 receptor which is responsible for :
1-plasma exudation
2-mucous secretion
3-Esionphilis recurmnet
4- B. C
-uses : as adjuvant drugs For BA, and ita a replacement for Glucocorticoids in children bcs the glucocorticoids cause growth retardation
———-
2-Mast cells stebiliazer
-Drug : Cromoglicic acid ~ Caps for inhalation
-mechanism: they block Ca2+ entry to the mast cell which lead to membrane stiblazation and inhibit the degranulation
-Pharmacokinetics: poorly absorbed in GIT
-uses : only for pervntation - side effect : Res tract irritation
——
3- Monoclonal antibodies MABs ( long term every 1 mothe )
-Drugs : Omalizumab Amp S.c
-mechanism: its antagonist of IGE which is binding to the mast cell , and degranulation , so this drug inhibit the Ige
-Drug : benralizumab Amp S.c
-mechanism : Via its Fab fragments, benralizumab specifically binds to IL-5Rα, thereby preventing the interaction between IL-5 and its receptor - Uses : As adjuvant drug For BA
