Pharmacology Drugs PDF

(By Vincent Dietrich) Overview: 3. Colloqium: 1. Colloquium: 3.1. Antipsychotics 1.1. Adrenergic agents 3.2. Antidepressants 1.2. Cholinergic agents 3.3. Antiepileptics 3.4. Antip...

(By Vincent Dietrich) Overview: 3. Colloqium: 1. Colloquium: 3.1. Antipsychotics 1.1. Adrenergic agents 3.2. Antidepressants 1.2. Cholinergic agents 3.3. Antiepileptics 3.4. Antiparkinsonian agents 2. Colloquium: 3.5. Analgesics 2.1. Antiplatelets 3.6. Anesthetics + Anticoagulants, + Thrombolytic agents 4. Colloqium: 2.2. Antihemorrhagic agents 4.1. Hypothalamic-pituitary 2.3. Diuretics hormones and agents 2.4. Antihypertensive agents 4.2. Bone mineral metabolism 2.5. Antianginal drugs 4.3. Antidiabetic drugs 2.6. Cardiac failure drugs 4.4. Reproductive system affecting 2.7. Antiarryhtmic drugs drugs 4.5. Genitourinary agents 5. Colloqium: 5.1. Steroidal anti-inflammatory 6.3. Oncology/ Chemotherapeutic agents agents + Targeted anticancer 5.2. Immunomodulators agents 5.3. Respiratory system affecting 6.4. Hematological agents drugs 5.4. Gastroenterological affecting drugs 5.5. Anti-glaucoma agents + Dermatologic agents 6. Colloquium: 6.1. Antibacterial drugs 6.2. Antifungals + Antiviral chemotherapeutic drugs + Antihelmintics 1) Adrenergic agents 2) Cholinergic agents  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Adrenergic Agents Adrenopositive (adrenomimetic/sympathomimetic) agents Epinephrine 1. Vasoconstrictive/dilatory Anaphylactic shock (adrenaline) Nonselective 1,2, 1,2 -> dose dependent Asystole adrenoreceptor agonist 2. Cardiotonic Topically + local -> + Inotropic anesthetics (Lidocain) -> + Chronotropic -> + Dromotropic 3. Bronchodilator 4. Mydriatic action 5. Low dose -> 1,2 6. High dose -> 1+1 7. Metabolic effect (Glycogenolysis) 8. Local hemostatic effect Norepinephrine 1. Vasoconstrictive Acute hypotension (Noradrenaline) Nonselective 1,2, selective 1 2. Cardiotonic -> collapse SBP + Inotropic 3. Mydriatic effect 4. Reflector Bradycardia -> Barorec. Stim. due to periph. Vasoconstriction 5. No bronchodilation ! Phenylephrine 1. Local action vasoconstriction Acute rhinitis, nose Recommended therapy not more than 5-7 days Selective 1 adrenoreceptor -> nasal decongestant bleeding -> Hypoxia/atrophy agonist 2. Systemic vasoconstrictive Acute Hypotension effect Paroxysmal ventricular -> Hypertensive effect tachycardia 3. Reflector – chronotropic effect 4. Mydriatic effect  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) Clonidine 1. Central hypotensive effect Hypertension Rebound effect Selective 2 adrenoreceptor -> Vasomotor center Hypertensive crisis -> BP agonist -> Stim. presyn. 2 receptor -> SANS stim. -> perip. Vasodil. Co-analgesia 2. Bradycardia effect 3.  Brain subcortical pain transmission => Co-analgesia Salbutamol 1.  intracellular Ca2+ conc. Bronchial asthma attack Tremor IA: Selective 2 adrenoreceptor 2. Relaxation of bronchial smooth Tachycardia (2 in heart) -  effect of agonist Muscles Tocolysis vasoconstrictive agents => Bronchodilation => Tocolytic effect (Inhib. of uterus contraction) Isoprenaline / Isopreterenol Nonselective  adrenoreceptor agonist Adrenonegative (adrenoblocking/sympatholytic) agents Doxazosin Selective 1 adrenoreceptor 1. Periph. vasodilation Hypertension First-dose orthostatic antagonist/blocker ->  periph. Resistance (afterload) hypotension + ->  vein capacity (preload) Symptomatic therapy of syncope, reflector ->  BP prostate adenoma tachycardia => Hypotensive effect 2.  Urethral tone + relaxes prostate muscle =>  urination disorders  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) Propranolol Coronary artery disease Bradycardia Prolonged 1st generation Tachycardia, AV block therapy causes Nonselective 1,2 adrenoblocker Thyrotoxicosis Bronchial obstruction adrenoreceptor Migraine attack Sexual dysfunction up-regulation prevention Raynaud syndrome -> leading to rebound effect after therapy Atrial Fibrillation (Class 2 stop antiarrhytmics) IA: - may affect effects of adrenopositive agent Timolol (eye drops) 1.  intraocular fluid secretion in Glaucoma Nonselective 1,2 adrenoblocker ciliary body ->  intraocular pressure -> does not affect drainage of fluid Metoprolol 1. Highly cardioselective 1 Coronary artery disease Treatment: Bisoprolol 2nd generation -> safer for asthma, DM, Hypertension 1. Glucagon Cardioselective 1 Raynaud syndrome patients Atrial fibrillation (Class 2 2. Calcium chloride adrenoblockers 2.  Vasoconstric. antiarrythmics) 3. Insulin ->  cardiac output Chronic heart failure 4. Sodium ->  SV Migraine attack bicarbonate prophylaxis 5. Vasopressors Carvedilol 1. Cardiodepressant Chronic heart failure 3rd generation (Cardioprotective) Coronary artery disease  , 1,2 adrenoblockers 1 ->  peripheral vascular resist. Hypertension -> antioxidant properties  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6)  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Adrenergic Agents Cholinopositive (cholinomimetic/parasympathomimetic) agents Pilocarpine 1. Fast, short term, non-selective Glaucoma, Glaucoma M cholinoreceptor agonist 2. Miotic effect attack -> m. sphincter p. contraction (pupil narrows) Xerostomia (Sjögren’s -> M. ciliaris contraction syndrome) (accommodation) ->  intraocular flow of fluid through Schlemm canal =>  intraocular pressure 3. Secretory effect -> salivation – main function Neostigmine 1. ACh degrading enzyme Myasthenia Exacerbation of chronic Treatment of toxic Piridostigmine Peripheral nonselective reversible inhibition GIT atony diseases: effects: acetylcholinesterase inhibitor -> prolongs/intensifies ACh Urinary bladder atony - Asthma, COPD, 1. Atropine activity at nACh + mACh Hyperthyroidism, Gastric ulcers, (antimuscarinic) (AChE-I) synapses Overdose or peripheral Parkinsonism (Carbamine acid esters) 2. Pralidoxime 2. Does not cross muscle relaxants (enzyme reactivator) hematoencephalic barrier Poisoning symptoms:  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) Cholinonegative (cholinoblocker/cholinolytic/anticholinergic) agents Atropine 1. Non selective mACh receptor Symptomatic sinus Tachycardia CI: (Atropa belladonna) M cholinoreceptor antagonist Blocker bradycardia (AV block) Xerostomia - closed angle glaucoma 2. Antisecretory Preoperatively, Blurred vision - prostate hypertrophy 3. Long term mydriatic - paralytic ileus suppression of -> enlarges pupil hypersecretion => Toxicity !!! IA: 4. Cycloplegic Antidote – poisoning with - antagonistic effect -> paralysis of accommodation insecticides against M-cholinomimetics 5. Antispasmodic GIT spasms + anticholinesterases -> relaxes smooth muscles 6.  Heartrate -> + chronotropic, + dromotrop. 7.  dose -> CNS excitement Botulinum toxin 1. Local ACh release inhib. in Post-stroke hand Acetylcholine release inhibitor presynap. Vesicles of periph. spasticity, Cerebral palsy Motoneurons spasticity -> hydrolyzes synaptobrevin Spastic cervical spine => Myorelaxation Blepharospasm Hyperhidrosis in the armpit Cosmetic surgery Cholinonergic agents affecting motor function Nicotine Acute biphasic effect N-cholinoreceptor agonists -> low dose – stim. ganglionic Nn receptors -> high dose – block 1. Phase: Stim. of N-cholinorecep. - Salivation, nausea - Vomiting, diarrhea - Bradycardia - Miosis - Fast, shallow breathing  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) 2. Phase: Suppression of parasymp. receptors +  effect on sympathetic systems - Tachycardia - AS elevation followed by AS  - Breathing inhibition - Mydriasis - Psychomotor agitation Suxamethonium Biphasic action: Intubation of trachea /Succinylcholine N-cholinoreceptor agonist 1. Phase: Short surgical / -> depolarization (like ACh) manipulations Depolarizing muscle relaxant 2. Phase: -> inhib of membrane repolariz. -> Cholinolytic effect occurs: => Myorelaxation 1. Choline ester resistant to ACh- esterase -> metab. By Butyrylcholinesterase Rocuronium 1. Non-depolarizing muscle Muscle relaxation during Antidote: N-cholinoreceptor antagonist relaxants /Anti-depolarizer surgical procedures - Sugammadex / (curare type) ACh antagonist Tubocurarine 1. Localization – neuromuscular N-cholinonegative agent synapsis 2. Affects depolarization of synaptic membrane Trimetaphan 1. Localization: Ganglia Ganglionic blocker Ganglioplegic  Pharmacology Drugs 1st Pharmacology Colloquium; Vincent Dietrich (V6) 1) Antiplatelets, Anticoagulants, Thrombolyic agents 2) Antihemorrhagic agents 3) Diuretics 4) Antihypertensive agents 5) Antianginal drugs 6) Cardiac failure drugs 7) Antiarryhtmic drugs  Antithrombotic (Antiplatelets, Anticoagulant, Thrombolytic agents), Hemostatic Agents and Diuretics 2nd pharmacology colloqu. Vincent Dietrich (V6) Antithrombotic agents Drug Pharmacological group Mechanism of action Clinical use Side effects Antiplatelets Acetylsalicylic acid Thromboxane synthesis Irreversible inhibition of COX1 -> à Secondary Bleeding from GIT NSAIDs reduce ASA (ASA, Aspirin) inhibitors (Antiplatelets) inhibition of thromboxane A2 cerebrovascular and binding to COX-1 synthesis cardiovascular thrombosis Blockade of platelet activation during prevention aggregate phase à ACS Antithrombotic effect Tirofiban GPIIb / IIIa receptor antagonist Platelet blockade in aggregation ohase à ACS (Antiplatelets) Antithrombotic effect Clopidogrel ADP receptor antagonist Block ADP receptor P2Y12 à Secondary prevention of NSAIDs, GC ­ risk of Indicated in case of aspirin (Antiplatelets) Blockade of platelet activation during cerebrovascular and bleeding intolerance aggregation phase cardiovascular thrombosis Prodrug activated via CYP450 (Liver) Irreversible receptor inactivation Indirect inhibition of GPIIb / IIIa receptor complex Ticagrelor ADP receptor antagonist Reversible P2Y12 receptor antagonist More rapid than Clopidgrel (Antiplatelets) Indirect inhibition of GPIIb / IIIa receptor complex Antithrombotic effect Anticoagulant Heparin Non-selective indirect inhibitor Forms complex with AT III à Deep vein thrombosis Hemorrhage Monitoring required of coagulation factors ­ AT III activity prevention and therapy Heparin induced Antidote: protamine (High molecular weight Indirect inhibition of Xa and IIa à ACS thrombocytopenia sulphate Heparin) coagulation factors Inactivate IXa, Xia, XIIa Antithrombotic effect Enoxaparin Non-selective indirect inhibitor Forms complex with AT III à Prevention of venous No monitoring of therapy of coagulation factors ­ AT III activity thromboembolism or dose adjustment (Small molecular weight Indirect inhibition of Xa and IIa à ACS required Heparin) coagulation factors (mainly Xa 2:1,4:1) Antithrombotic effect Fondaparinux Selective indirect inhibitor of Forms complex with AT III factor Xa ­ AT III activity Indirect inhibition of Xa Antithrombotic effect Rivaroxaban Selective direct inhibitors of Irreversible, free and thrombus-bound à DVT and Pulmonary Antidote: andexanet alfa Apixaban factor Xa inhibition of factor Xa embolism treatment  Antithrombotic (Antiplatelets, Anticoagulant, Thrombolytic agents), Hemostatic Agents and Diuretics 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacological group Mechanism of action Clinical use Side effects - Xa activates prothrombin via thrombin à Prevention of recurrent Antithrombotic effect DVT and PE à Stroke prevention (Afib) Dabigatran Selective direct inhibitor of Reversible inhib. of factor IIa à DVT and PE prevention Antidote: Idarucizumab factor IIa (thrombin) (hip, knee prosthesis) Inhib. of IIa is secondary to inhibition à Stroke prevention (Afib of fibrinogen activation of fibrin Prevents thrombin assoc. PLT aggreg. Antithrombotic effect Warfarin Vitamin K antagonist Inhibits vit. K epoxide reductase à DVT and PE treatment + Therapeutic effect only Inhibits synthesis of prothrombin, prevention after 5 days factors VII, IX,X à Secondary prevention of Warfarin has no effect on Antithrombotic effect MI + thromboembolic pre-synthesized Inhibits protein C and S complication after MI coagulation factors à Stroke prevention (Afib) à Prevents thromboembolic complications In heart valve diseases / prosthetic Thrombolytic agent Alteplase Plasminogen activator Activation via binding to fibrin à Pulmonary Embolism Conversion of plasminogen to plasmin à ACS Promotes dissolution of fibrin clot à Ischemic stroke therapy Fibrinolyitc effects Antihemorrhagic agents Tranexamic acid Fibrinolysis inhibitor Reversible, lysine domain blockade in à Complications of Seizures at high dose plasminogen fibrinolytic therapy or Risk of thrombosis when -> inhib. of plasminogen activation hyperfibrionolysis combined with oral Prevents binding of plasmin to fibrin à Present/Prognosed contraceptives and its degradation Massive bleeding Inhibits plasmin activity at high dose Preserves PLT functionality Antifibrinolytic effect Desmopressin Vasopressin receptor agonist V2 receptor agonist in endothelium à Scheduled surgery in ­ coagulation factor VII patients with hemophilia ­ von Willebrand factor in plasma A or von Willebrand’s ­platelet adhesion in endothelium disease Antihemorrhagic effect à Bleeding control in patients with prolonged blood flow time  Antithrombotic (Antiplatelets, Anticoagulant, Thrombolytic agents), Hemostatic Agents and Diuretics 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Diuretics Mannitol Osmotic diuretics Causes osmotic diuresis à Increased intracranial Dehydration -> inhib. H2O reabsorption !! pressure Electrolyte imbalance -> inhib. Na+ reabsorption in à Acute glaucoma attack proximal renal tubulues and henle loop à Acute renal failure forced => Diuretic effect diuresis Stim. Return of intraocular fluid to plasma -> Anti-glaucoma effect Acetazolamide Carbonic anhydrase inhibitor Inhib. of carbonic anhydrase à Edema Metabolic acidosis Tolerance develops in 2-3 -> no carbonic acid synth. In prox. à Glaucoma, acute attack days of use Renal tubules à Acute mountain sickness -> ­ release if water and Na+ (AMS) -> ­ HCO3- excretion => Diuretic effect ¯ intraocular fluid production => anti-glaucoma effect Furosemide Loop diuretics Inhib. of Na+/K+/2Cl- transporter in à Chronic heart failure Hypokalaemia Fast acting w/ risk of (­ dose -> ­ effect) ascending part of loop of henle à Arterial hypertension Hypocalcaemia hyperkalemia Torasemide -> ­Na,K,Cl,Mg, Ca secretion à Edema due to liver / kidney Ototoxicity (ear) Slow acting => Diuretic effect à Swelling of lungs, brain, ¯ of circ. Blood volume -> ¯ BP burns => Hypotensive effect Hydrochlorothiazide Thiazide diuretics Inhib. of Na+/Cl- transporter in distal à CHF Hypokalaemia Interaction with NSAIDs Indapamide Thiazide like diuretic renal tubule à AH -> ­Na,K,Cl,Mg secretion à Kidney stone disease -> ¯ Ca, uric acid secretion caused by hypercalciuria => Diuretic effect ¯ of circ. Blood volume -> ¯ BP => Hypotensive effect  Antithrombotic (Antiplatelets, Anticoagulant, Thrombolytic agents), Hemostatic Agents and Diuretics 2nd pharmacology colloqu. Vincent Dietrich (V6) Spironolactone Potassium sparing Diuretics Block aldosterone receptor in renal à CHF Hyperkalaemia Interaction with ACE Eplerenone (weak) tubules à Resistant arterial Gynecomastia inhibitors Mineralocorticoid / aldosterone -> Nuclear regulatory aldosterone hypertension (antiandrogenic effect) receptor antagonist induced inhibition of protein à Primary synthesis -> ¯ Na+ channel hyperaldosteronism expression in collecting duct (Spironolactone) Block aldosterone receptor in à Hirsutism, acne myocardium and blood vessels (Spironolactone) => Mild diuretic effect => Antifibrotic effect => Antiandrogenic effect (Spironolactone)  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antihypertensive agents Enalaprilat Angiotensin converting enzyme ACE inhibition à Arterial hypertension Dry cough Captopril (ACE) inhibitor Venous and arterial vasodilation à Arterial Hypertension Hyperkalaemia Enalapril => ¯ pre and after load à CHF Teratogenic (embryonic Primary drug group Perindopril => Hypotensive effect à Coronary heart disease affecting) ¯ Cardiovascular remodelation à Diabetic nephropathy ¯ aldosterone secretion (Captopril) Valsartan Angiotensin receptor AT1 blocker Blocks angiotensin II binding to AT1 à Arterial Hypertension Hyperkalaemia Candesartan (ARB) receptor à Chronic heart failure Teratogenic Losartan Venous and arterial vasodilation Primary drug group => ¯ pre and after load => Hypotensive effect ¯ Cardiovascular remodelation ¯ aldosterone secretion Nifedipine Calcium channel blocker Arterial vasodilation à Arterial hypertension Constipation Amlodipine (dihydropyridine) -> ¯ after load à Prevention of stable angina Peripheral edema Nicardipine No Ca2+ and calmodulin binding pectoris attack (ankles) Primary drug group -> smooth muscle relaxation à Coronary heart disease (vasospastic form) Metoprolol Beta Adrenoblockers ¯ CMV (¯ HR, Contractility) 1. 2. Generation can Bisoprolol ¯ Renin secretion cause reflex Nebivolol Peripheral arterial vasodilation vasoconstriction Primary drug group Carvedilol Labetalol Hydrochlorothiazide Diuretic agents Reduce volume of circulating blood Indapamide via nephron Primary drug group Furosemide ! See diuretic table ! Long term affect on vascular smooth Spironolactone muscle Doxazosin Alpha1 selective adrenoblocker Vasodilation of arteries and veins à Arterial hypertension First dose orthostatic -> ¯ perip. resistance (¯ postload) hypotension and Secondary drug group -> ­ vein capacity (¯ preload) syncope - peripherally acting ¯ BP => Hypotensive effect Reflector tachycardia Moxonidine Selective Imidazoline I1 receptor ¯ SNS activity (receptors mainly in à Arterial hypertension + Secondary drug group agonist (SIRA) medulla oblongata) metabolic syndrome - centrally acting ¯ BP Clonidine Central Imidazoline1 and alpha 2 à Antihypertensive therapy Bradycardia Secondary drug group adrenoreceptor agonist in urgent situations Sedation - centrally acting Dryness in mouth Metyldopa Inhibits dopa-decarboxilaze à Gestational hypertension Secondary drug group Stim. Presynaptic alpha 2 receptor - centrally acting  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Emergency and urgent situation medication Sodium NO-modulator Direct action vasodilator à Hypertensive emergencies nitroprusside NO donor ->­cGMP -> ¯ pre/afterload Short acting Labetalol Alpha and beta adrenoreceptor à Hypertensive emergencies antagonist and urgencies Drug Pharmacology group Mechanism of action Clinical use Side effect Antianginal drugs Glycerilnitrate Organic nitrates (Nitrate donor) Venous (small dose) and periph. à Current Angina attack Headache, hypotension, (GNT) arterial dilation (high dose) reflex tachycardia Isosorbide => Antianginal, Hypotensive effect à Prevention of angina Interaction with PDE5 mononitrate (GNT Dilation of coronary blood vessels attack inhibitors -> Hypotension metabolite) => Antianginal effect NO -> ­ cGMP -> BV relaxation Nifedipine Calcium channel blockers Dilation peripheral arteries à Prevention/prophylaxis of Headaches, facial Amlodipin Dihydropiridine => Antianginal, hypotensive effect angina attacks flushing, fatigue ! Calcium channel blocker ! see in antihypertensive agents ! Coronary artery dilation à Prevention of vasospastic Peripheral edema, toxicity => Antianginal effect angina attack constipation Verapamil Calcium channel blockers Reduce CMV (HR and contractility) à Prevention/prophylaxis of Diltiazem Non-dihydropyridine => cardiac depressant effect angina attacks Peripheral arterial dilation à Prevention of vasospastic Coronary artery dilation angina attack ! Calcium channel blocker Diastole prolongation toxicity => Antianginal, hypotensive effect Reduce AV conduction => Antiarrythmic action Propranolol Beta blockers => Cardiodepressant effect à Prevention / Prophylaxis of Bradycardia, AV block Metoprolol, ¯ CMV (HR, Contractility) during rest angina attacks Bronchospasm Bisoprolol and physical activity Cold extremities => Antianginal, hypotensive effect Prolong diastole => Antianginal effect Reduce AV conduction => Antiarrythmic effect  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Ivabradine Sinus Node Inhibitor (bradine) Inhibits Na+ flow in the sinus node à Prevention / Prophylaxis of Light phenomena in ¯ HR (dose dependent) stable angina attack retina Prolong diastole (­ O2 supply) Pronounced bradycardia => Antianginao effect No vasoconstriction and no contractility Ranolazine Late Sodium flow inhibitor Late blockade of Na+ channels Sodium (Na+) channel blockers ¯ intracellular Ca2+ -> ¯ myocardial diastolic tension -> ¯ O2 consumption Drugs for prevention of adverse cardiovascular events Atorvastatin HMG-coenzyme A reductase Blocks mevalonic acid synthesis in à Dyslipidemias Hepatic function inhibitor liver (cholesterol precurs.) à Prevention of impairment ­ LDL receptor expression in cardiovascular events Myopathy hepatocytes -> ¯ LDL in plasma Fenofibrate PPAR-alpha agonist LPL gene expression -> Serum lipoprotein lipase activation Lipolysis -> ­ LDL recept. In hepatoc. Hypolipidemic (lipid-correcting) Ezetimibe Cholesterol absorption inhibitors Inhibits cholesterol absorption In agents small intestine -> ¯ LDL Evolocumab PCSK9 inhibitor Inhibition of LDL receptor-degrading enzyme -> ¯ serum LDL cholesterol Acetylsalicylic acid Clopidogrel Antiplatelets Ticagrelor Tirofiban ACE inhibitors RAAS blockers ARB  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Cardiac failure drugs Captopril ACE inhibitors Artery and vein dilation à CHF Enalapril Antifibrotic, Delay of remodeling Ramipril (RAAS activity reducing agents) Valsartan Angiotensin 2 AT1 receptor Candesartan blockers (ARB) Losartan (RAAS activity reducing agents) Valsartan + ARB + Neprilysin inhibitor (ARNI) Artery and vein dilation à CHF Effects Natriuretic peptide Sacubitril (always in combination) ¯ Heart load ¯ circulatory volume Antifibrotic, Delay of remodeling Metoprolol Beta blockers Artery and vein dilation (only 3rd) à CHF Bisoprolol (2nd) Heart performance enhancing effect Nebivolol, -> negative chronotropy Carvedilol (3rd) Antifibrotic, Delay of remodeling Spironolactone Mineralocorticoid receptor ¯ Heart load à CHF Hyperkalaemia, (nonselective) antagonist (aldosterone receptor -> ¯ of circulating volume gynecomastia Epleronone antagonist) (MRA) Antifibrotic, delay of remodeling (selective) Antiandrogen effect (Spironolactone) Dapagliflozin Sodium/glucose co-transport SGLT-2 inhib. in renal proximal à CHF Urinary tract infections Empagliflozin protein 2 (SGLT2) inhibitor tubules NHE-1 inhib. in heart SGLT-1 inhib. in heart => ¯ body weight Artery dilation => Heart load reduction Antifibrotic , delay of remodeling Hydrochlorothiazide Thiazide diuretic K+ excreting à CHF Hypokalaemia Indapamide Thiazide like diuretic ¯ circulatory volume Furosemide Loop diuretic à AHF, CHF Hypokalaemia, Hypocalciaemia Ototoxicity Ivabradine Sinus node inhibitor Heart performance enhancing à CHF -> negative chronotropy Heart lode reduction  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Inotropic agents Digoxin Cardiac glycoside Inhib. of Na+/K+ pump in à AHF, CHF 70% overdose -> rhythm Cardiac glycoside toxicology cardiomyocytes -> ­ intracellular disorder !! Ca2+ Risk of drug “+” inotropic effect (contractility) accumulation “-“ chronotropic effect (HR) => Heart performing enhancing Heart load reduction Dobutamine Beta 1 adrenoreceptor agonist “+” inotropic effect à AHF mild “+” chronotropic effect => heart performance enhancing effect Dopamine D1, beta 1, alpha 1 receptor Low dose: agonist ­ renal microcirculation Medium dose: “+” inotropic effect High dose: Vasopressor effect Levosimendan Calcium channel sensitizer “+” inotropic effect (without ­O2 à AHF consumption) => Heart performing enhancing effect Vasodilation Cardioprotection => Heart load reduction Milrinone PDE-3 inhibitor Inhibition of phosphodiesterase-3 à AHF “+” inotropic effect => Heart performance enhancing effect Vasodilation => Heart load reduction Glyceryl trinitrate NO donors Artery dilation at high dose à AHF Sodium Venous dilation at low dose nitroprusside => Heart load reduction Additional agents for treatment of AHF Morphine Opioid receptor agonist ¯ tachypnoea Norepinephrine Vasopressor agents in hypotensive patients  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antiarrhythmic drugs Procainamide Class I(A) Na+ channel blocker with medium à Treatment of Hypotension dissociation kinetics supraventricular Lupus erythematodes -> delays Na+ flux in phase 0 by arrhythmias (SVA) syndrome expanding QRS à Treatment of ventricular K+ channel blocker arrhythmia (VA) -> inhib. K+ in phase 3 by expanding QT interval => Proarrhythmic effect Lidocain Class I(B) Na+ channel blocker with fast à Treatment of VA CNS toxicity (seizures) First-pass metabolism (do dissociation kinetics not use p / o) -> delays Na+ flow in phase 0 -> but QRS remains unchanged Propafenone Class I(C) Na+ channel blocker with slow à SVA (including control of Heart failure Flecainide dissociation kinetics Afib) Ethacizine -> delays Na+ flux in phase 0 by expanding QRS K+ channels and repolarization are not affected Propranolol Class II Beta 1 block in SA and AV node à Frequency control of SVA Metoprolol (Beta blocker) Delays Ca2+ in SA phase 0,4 (Afib, sinus tachycardia) Bisoprolol -> prolongs RR interval à VA treatment -> “-“ chronotropic effect Inhib. Ca2+ in AV phase 0 and 4 -> prolongs PR interval -> “-“ dromotropic effect Inhib. Ca2+ in CM phase 2 -> “-“ inotropic effect Amiodarone Class III K+ channel blocker à SVA (including Afib) Hypothyroidism Amiodarone toxicology -> inhib. K+ in phase 3 à VA treatment Pneumofibrosis -> prolonges QT interval Phototoxicity Na+ channel blocker Heaptotoxicity -> inhib. Na+ in phase 0 Blue skin pigmentation -> expands QRS complex (smurf skin) Beta blocker Corneal depositions -> (same as Class II) Rarely TdP Calcium channel blocker  Antihypertensive, Antianginal, Cardiac failure and Antiarrhythmic drugs 2nd pharmacology colloqu. Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect -> same as beta blocker ! Vernakalant Class III K+ channel blocker à Acute Afib treatment Hypotension -> inhib. K+ in phase 3 Bradycardia -> prolonges QT interval Na+ channel blocker with fast dissociation kinetics -> inhib. Na+ in phase 0 -> but QRS complex unchanged Verapamil Class IV Ca2+ channel blockade à Frequency controle of SVA Diltiazem (Ca2+ channel blocker) -> same effect as Class II (Afib, sinus tachycardia) Non-classified antiarrhythmic agents Magnesium sulfate ¯ Ca2+ flow in ventricular à Torsade de pointes (TdP) cardiomyocyte treatment Atropine “+” chronotropic effect à Sinus bradycardia “+” dromotropic effect à AV node block Epinephrine “+” inotropic effect à CPR “+” chronotropic effect “+” dromotropic effect Digoxin “+” Inotropic effect à SVA rhythm disorders K+, Mg+ aspartate given as “-“ chronotropic effect (Afib) prophylaxis against “-“ dromotropic effect overdose -> reflectory increasing n.vagus tone Can be used with BAB or CCB 1) Antipsychotics 2) Antidepressants 3) Antiepileptics 4) Antiparkinsonian agents 5) Analgesics 6) Anesthetics  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antipsychotics Haloperidol Typical / 1st generation D2 > 5HT2A Schizophrenia Typical Chlorprothixene Acute Mania pharmacological Quetiapine Atypical / 2nd generation 5HT2A > D2 Schizophrenia profile of AP Olanzapine Bipolar disorder generations Aripiprazole Atypical / 2nd generation D2 partial agonist Schizophrenia Pharmacological § delayed reg. of Acute Mania profiles different from dopaminergic system in Bipolar disorders generation profile mesocortical tract 5-HT2A antagonist Clozapine Atypical / 2nd generation D4 > 5HT2A > D2 Treatment-resistant Agranulocytosis schizophrenia Risk of convulsion Severe constipation Melperone Not assigned to spec. Gen. D2 receptor blockade Schizophrenia Rarely causes EPS (like Neurotic states, States of 2nd gen.) confusion (seniors) Sulpiride Not assigned to spec. Gen. Does not affect 5HT2 receptors Schizophrenia Rarely causes EPS (like Low dose: Treatment of depressive 2nd gen.) -> negative symptomatology disorders and mood symptomatology  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antidpepressants (Mood influencing agents) Lithium carbonate Mood stabilizers (Normotimic Influences 2nd signalling: Bipolar disorders (BD) Tinnitus o Adequate renal + Carbamazepine agents) 1) Inhib. of cascade of IP3 and Aphasia function needed + Valproic acid DAG signals Visual disturb. + Lamotrigine -> inhib. inositol Hypothyrodism monophosphate Inhib. ADH 2) Inhib. glycogen synthetase kinase 3 (GSK-3) ¯ cation transp. through cell membranes in neurons and myocytes => ¯ manic and depressive phases => Stabilizes patients mood Amitriptylin Non selective monamine Inhib. SERT / NET Major depression Overdose: (3Cs) reuptake inhibitors (NMRIs) (Serotonin reuptake Chronic neuropathic pain Cardiotoxicity / Tricyclic antidepressants transporter / NE) Convulsion Antagonizes receptors: Coma - 5-HT2 - H1 Contraindication: - M1-5 Glaucoma Blocks alpha-1 recept. => antidepressant effect => sedative effect => co-analgesic effect Duloxetine Selective Serotonin and Inhib. SERT and NET Major depression Nausea o Interaction with Venlafaxine Norepineprhine Reuptake Generalized anxiety Vomiting MAOI – serotonin inhibitors (SSNRIs) => Antidepressant effect disorder Sexual dysfunction syndrome => anxiolytic effect Chronic neuropathic pain => co-analgesic effect  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Paroxetine Selective Serotonin Reuptake Selective SERT inhib. Major depression Nausea o Interaction with Citalopram inhibitors (SSRIs) Obsessive compulsive Vomiting MAOI – serotonin Sertraline => Antidepressant effect disorder Sexual dysfunction syndrome => anxiolytic effect Panic, anxiety o Risk of Phobias hemorrhage with new gen. anticoagulants Bupropion Selective dopamine and Inhib. Dopamine reuptake Major depression Seizure norepinephrine reuptake transporter (DAT) and NET Smoking cessation ¯ weight inhibitors (SDNRI) Inhib. CytP450 2D6 => Antidepressant effect => CNS stim. effect Mirtazapine Noradrenergic and specific Antagonist for: Major depression Weight gain o Serotoninergic Antidepressants Presyn. a2-receptor sedation (NaSSA) -> ­ NE, 5HT release at synap. / tetracyclic antidpepressant 5HT2, 5HT3 H1 receptor => Antidepressant effect => Sedative effect Anxiolytics, Sedatives and Hypnotics Diazepam Long acting Benzodiazepine (BZD) => Anxiolytic effect Sedation (premed. For Anterograde amnesia -> T1/2 24h => muscle relaxant surgical procedures) Drowsiness => anticonvulsant effect Anxiety sleep disorder Respiratory depression Medication to treat seizure onset => Sedative effect Muscle spasms => Hypnotic action seizures Midazolam Short acting Benzodiazepine Introductory anesthesia (BZD) Premed. For diagnostic or -> T1/2 1.5-2.5h therapeutic manipulation Seizures Medication to treat seizure onset Alprazolam Benzodiazepine => Anxiolytic effect Panic attacks Contraindication: (Xanax) -> T1/2 11h => muscle relaxant Anxiety Driving => Sedative effect Stress symptomatic => Hypnotic action therapy  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Phenobarbital Barbituric acid derivates / 1) Affects Cl- channel of GABA A Cardiac neurosis Dependence, addiction o Induction of Barbiturates complex Vegetative agitation problem cytochrome CYP (Non-benzodiazepines) -> GABA A recept. Antagonist Sleep disorder -> Barbituromania enzymes 2) GABA A + allosteric modulator Epilepsy Medication to treat seizure onset -> binding beta subunit -> prolong GABA action Zolpidem Benzodiazepine analogs Association with GABA a1- Short term treatment of Somnambulism subunit sleep disorders Hallucinations -> not in all complexes => Hypnotic effect  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antiepileptics Valproic acid Epilepsy control agents Blockade of voltage dependant Generalized epilepsy Teratogenic activity NalCaCT) Na+ and Ca2+ channel in -> tonic-clonic Medication to treat seizure onset neurons -> absence Gaba Bansaulivare Inhib. GABA transaminase Focal epilepsy -> prolong GABA activity Status epilepticus Bipolar disorder => Anticonvulsant effect (control) => mood stabilization Ethosuximide Epilepsy control agents Blockade of Ca2+ channels in Block 2a(t) neurons => Anticonvulsant effect (control) Lamotrigine Epilepsy control agents Blockade of voltage dependant Generalized epilepsy Bluck Na and Na+ and Ca2+ channel in -> tonic-clonic neurons -> absence 2a(NIPG) Focal epilepsy => Anticonvulsant effect (control) Bipolar disorder => mood stabilization Carbamazepine Epilepsy control agents Blockade of voltage dependant Generalized epilepsy Block Na Na+ channel in neurons -> Tonic-clonic Bipolar disorder => Anticonvulsant effect (control) Neuropathic pain => mood stabilization (trigeminal neuralgia) => co-analgesic effect Gabapentin Epilepsy control agents Analogue of GABA Focal epilepsy raa structipal Inhib. of voltage-sensitive Ca2+ Neuropathic pain channels -> diabetic neuropathy analog -> postherpetic neuralgia => Anticonvulsant effect (control) Chronic Pain syndrome Block 2a (NIPG) => Co-analgesic effect  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Levetiracetam Epilepsy control agents Binds synaptic vesicle protein Generalized epilepsy SVPZ 2A -> Tonic-clonic Medication to treat seizure onset Affects neurotransmitter Focal epilepsy exocytosis Status epilepticus Topiramate Epilepsy control agents 1) Blocks Kainate/AMPA recept. Generalized epilepsy AMPAI Kaincie 2) Blocks voltage dep. Na channel -> Tonic-clonic Bluck Na Ca(N(PR) 3) Blocks Ca2+ channels Focal epilepsy GABA A allosterie modulator (1) 4) GABA-A receptor allosteric modulation  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Antiparkinsonian agents Levodopa (L-Dopa) Dopamine precursor and Can cross BBB Parkinson disease L. tolerance (motor dopamine receptor agonists Converting L-Dopa to Parkinsonism (except one complications after 5y. -> Dopamine prodrugs dopamine in nigrostriatal tract caused by antipsychotics) of usage) -> restores neurotransmission -> Wearing off effect: => reduces EPS - episodic exacerbation -> On-Off effect: - acute cycles of exacerbation throughout day Levodopa-induced dyskinesia (LID) -> involuntary movement during on-time -> bradykinesia during off- time Carbidopa, Dopamine precursor and Are Decarboxylase Inhibitors Benserazide dopamine receptor agonists Do not cross BBB -> dopamine prodrugs Peripheral Levodopa inhibitors of metabolism ¯ dopamine induced GI side effects (nausea, vomiting) ¯ Cardiovascular side effects (arrythmias, Hypotension) Pramipexole Dopamine precursor and Non-selective agonists of dopamine receptor agonists striatal dopamine D2 receptors Parkinson’s Disease Selegiline MAO-B inhibitors Inhib. enzyme MAO-B, which Hyperprolactinemia (only (Monoamine oxidase-B inhib.) breaks down dopamine bromocriptine) -> ­ dopamine availability Entacapone not cross BBB COMT inhibitors Tolcapone cross BBB  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Trihexyphenidyl Central acting choline blocker Central M1 choline blocker Parkinsonism Dopamine acts as Ach Blocks Ach-induced EPS Correction of EPT induced antagonist antipsychotic agents -> in case of D- deficiency Ach can cause EPS Amantadine NDMA receptor antagonist Suppresses glutamatergic Parkinson’s Disease activity Promotes dopamine synthesis + secretion Inhib. dopamine presynaptic uptake Anti-dementia agents Donepezil Acetylcholinesterase inhibitor ¯ symptoms of Alzheimer’s dementia Cholinergic IA: neurodegeneration Vascular dementia hyperactivity Medicines with slows cognitive decline Parkinson’s dementia anticholinergic properties Memantine Glutamate NMDA receptor Alzheimer’s dementia channel blocker / antagonist  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Analgesics Morphine Opioid receptor agonist µ,d,k recept. Agonists Traumatic pain relief M, S, Postoperative pain agonist r => analgesic effect Tumor-induced pain => sedative effect Codeine Opioid receptor agonist Weak µ recept. Agonist Moderate intensity pain wean Resp. depression Magonist => analgesic effect Nausea, vomiting => sedative effect Suppression of cough reflex Fentanyl Opioid receptor agonist µ,d recept. Agonist Tumor pain Pupil constriction M, S Partial k recept. Agonist ­ in GI tone agonist Bradycardia, hypotension Patial => analgesic effect Itching 1 agonist (stronger than morphine) ­ tone of Oddi sphincter => sedative effect ­ urinary tone (short acting) Muscle rigidity Tramadol Opioid receptor agonist Weak µ affinity Moderate intensity pain Euphoria Tolerance weak M => analgesic effect Addiction agonist (enhanced by SNRI) Abstinence => sedative effect Buprenorphine Opioid receptor agonist Partial µ receptor agonist Abstinence of potent he partial k receptor antagonist opioid receptor agonist or agonist opiates R aniagonist => analgesic effect Sever to moderate pain => sedative effect Paracetamol Non-opioid analgesics Prostaglandin H2 synthetase Short-term treatment of Overdose: (“Acetaminophen) inhibitor moderate intensity Lethal (7-10g) Inhib. of COX2/3 in CNS postoperative pain i/v Liver failure, Inhib. of PG synthesis centrally Symptomatic treatment of encephalopathy, coma Central effect on proinfl. mild to moderate pain p/o Cytokine release Fever => Analgesic effect => Antipyretic effect with slight anti-infl. effect  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Metamizol Non-opioid analgesics Inhib. of COX in CNS (inhib. of Severe to moderate Agranulocytosis PG synthesis centrally) intensity postoperative / Antispasmodic effect post-trauma pain i/v Severe to moderate intensity acute pain p/o Fever Sumatriptan 5-HT receptor agonist Vasoconstriction of blood Migraine attack therapy vessel of brain Calcanezumab CGRP antagonist => analgesic effect Migraine attack prophylaxis Erenumab CGRP receptor antagonist Naloxone Opioid receptor antagonist Diclofenac Non-steroidal anti-infl. drugs Ibuprofen (NSAIDs)  CNS Pharmacology 3rd Pharmacology Colloquium; Vincent Dietrich (V6) Drug Pharmacology group Mechanism of action Clinical use Side effect Anesthetics Propofol Allosteric modulation of Maintenance of general GASSA receptors anesthesia => Sedative effect Induction anesthesia => Hypnotic effect Sedation Etomidate General anesthetic GABA-A allosteric modulation Induction anesthesia -> Non-inhalation => Sedative effect -> i./v. => Hypnotic effect Ketamine NMDA receptor channel Maintenance of general Cataleptic condition: -> eyes are open blocker anesthesia -> not communicative Analgesia Induction anesthesia Dissociative anesthesia Postoperative sedation Sevoflurane GABA-A receptor modulator Maintenance anesthesia Malignant (Volatile liquids) => anesthetic effect hyperthermia Tachycardia General anesthetic Resp. failure -> Inhalation Acidosis Rigidity Rhabdomyolysis Nitric oxide NMDA receptor antagonist Maintenance anesthesia (Gaseous substances) Release of endogenous opioid peptid