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, Contraction-urinary VASOCONSTRICTION Effect BP on stimulation/agonist Mydriasis-good in glaucoma Drug receptor selectivity Epinephrine> Norepinephrine >>>>>>>>> Isoproterenol
Blood Vessel Smooth Muscle-TPR (skin) Pupil Radial muscle Intestine, Prostate, Bladder sphincter cAMPNorepinephrine Presynaptic release receptorNor(auto)/Ach(hetero) INHIBITORY Pancreatic cellinsulin Fat, Platelet HeartIno, Chrono, AV nodal conduction velocity JG cellsRenin
Dopamine
cAMP:adenylyl cyclase
adenylyl cyclase Open K channel Ca influx Cholinergic Nicotinic Agonist-small dose Nicotine Muscarinic Agonist-Muscarine Histamine H1
Blood Vessel SKELETAL, (coronary) Uterine Smooth muscle Respiratory Liver Pancreatic cell Ciliary muscle Fat cell Blood vessel-Smooth muscle: Renal, Splanchnic, CORONARY, Cerebral--RELAXATION Nerve terminal
Nor/Ach Neuromodulationinhibitory insulin & lipolysis (DOMINANT) Platelet aggregation BP, HR,conduction Reninfluid retentionvenous returnSVCOBP;Ang2TPRafterloadheart work,BP GIT smooth muscle relaxation Vasodilation Relaxation (tocolysis) Bronchodilation Glycogenolysis insulin (MILD) Relaxation-Mydriasis lipolysis Vasodilationblood flow (CORONARY)
BP on stimulation/agonist
blood flow to skeletal muscle/HEART air in lungs energy Good in glaucoma On stimulation/agonist
Norepinephrine release Autoregulator AchNorepinephrine at vasoconstrictor nerves AchM3NO/EDRF releasevasodilation (cavernous muscleerection) Sildenafril Smooth Muscle Contraction Blood Vessel: (Short Lasting) Vasodilation-NO, PG release capillary permeability, gap junction widening Smooth muscle: vasoconstriction-larger vessels Afferent Nerve Stimulation Gastric Gland-Gastric Acid Secretion Blood Vessels: (persistent) Vasodilation-smaller vessels Heart: +ve Chronotropy & +ve Inotropy, HR Presynaptic H3 Receptors-release several transmitters Skin of face, Neck, salivary Cholinergic glandsstimulate/agonistblushing drug-all vessels dilate Bronchoconstrict Sensory Nerve ion EndingsAllergies stimulation-pain Waking Amine Triple responseID Peptic Ulcer injectionRed spot, edema & flare BP(vasodilation ), sense of warmth, Headache
H2
H3
Gastric Parietal Cells Cardiac Muscle Smooth Muscle Brain Histaminergic Neurons Myenteric Plexus
Drug Epinephrine
Class Catecholamines
Effect 2-dilates coronaries & skeletal blood vessels-blood flow 1&2-consticts blood vessels of skin & mucosa
Norepinephrine
Isoproterenol
Dopamine
1=2 1>>>2 1,2,1 agonist 1=2>>>> Mainly ;Less D1=D2 >>1>> D1, , 1 agonist
1 vasoconstrictionTPR-BP
BP
Uses ANAPHYLACTIC SHOCK()(IM), local anaesthetic, GLAUCOMA(1), local bleed (nose)( 1&2) Physiological antagonist of Histamine Glauoma Heart block, cardiac arrest Local hemostasis(1) Shock Dopamine preferred Heart block, cardiac arrest
ADR/Interactions +COCAINECVS cardiac workeffects ischaemia, MI, heart failure BP HR Arrythmias Pulmonary edema
Low dose: Inotrope D1-vasodilation-renal, splanchnicblood to kidney, viscera D2-presynaptic autoreceptorNorepinephrine release Moderate dose: (D1) contraction,conduction (heart) High dose: vasoconstriction Vasoconstriction of nasal mucosa Topical-long acting Vasoconstriction Mydriasis
Selective Adrenergics
Nasal decongestants
Methoxamine Clonidine
methylDOPA
Dobutamine
Selective 2 agonist methyl analogue of DOPA (precursor of DA, NE) Selective(relatively) 1 1 agonist >2>>>
vessels
Inotrope
Selective 2 agonist
Cardiogenic/Septic Sinus tachycardia, Arrhythmia /Renal shock CHF-inotrope Post MI shock/pump failure Cardiac surgery Asthma Skeletal muscle tremors Premature labor Postural Hypostension Ma Huang-weight loss, appetite suppression Nasal decongestant CNS: tremors, anxiety, insomnia, convulsions, anorexia
Pseudoephederine Mephentermine INDIRECTLY Release ACTING Amphetamines: Dex/Met Amp, Modafinil, Methylphenidate Tyramine
Mixed acting adrenergic & agonist Indiectly acting adrenergic Norepinephrine release CNS, alertness weight
Drug of Abuse CNS: tremors, anxiety, insomnia, convulsions, anorexia Present in fermented food- cheese, wine, sausages Metabolized: Liver-MAO enzyme Drug of Abuse: Dopamine in brain neurons
Reuptake
Cocaine
Type blocker
Class Nonselective
Action 1 blockadeTPRCOBP Secondary shock-reflex vasoconstrictionhypovolemic shock CHF-short term relief Peripheral vascular disease
ADR/Interactions Postural hypostension-dizziness & syncope Nasal stuffiness-dilated blood vesselsextravasation Miosis-cholinergic-pupillae constrictor Diarrhea: cholinergic dominance Inhibition of ejaculation
Selecti ve
1 blocker
2 blocker blocker
Hypertension
Anticholinergic
Atropine
No marked effect on BP
H1 Blocker
Anti Allergic-(type 1 HS-Histamine) Allergic reactions-Allergic Rhinitis (hay fever), urticarial, Drug induced allergy (type 1 HS) Atopic Dermatitis: Dipenhydramine (sedative-reduces itchiness sensation) Parkinsonism: Dipenhydramine/inate, Promethazinetremor,rigidity(Anti Chloinergic) Pregnancy Nausea/Vomiting: Doxylamine, Promethazine Motion Sickness: Dipenhydramine/inate, Promethazine, Cyclizine, Meclizine Pomethazine: Vestibular Disturbances: Cinnarazine (AntiHistaminic, AntiCholinergic, Anti5HT)
vasodilation-2 blockade Renin-Ang2-TPR-BP-1 blockade Heart 1 blockade-CO-BP Normal dose-Blocks Ach agonistvasodepressor action (TPR; INDIRECT) Large dose: Direct Vasodilator AntiAllergic-(Histamine=type 1 S) Sedative Highly: Dipenhydramine/inate, Promethazine Moderately: Pheniramine, Cyproheptadine, Meclizine, Cinnarazine Anticholinergic: Dipenhydramine/inate, Promethazine AntiHistaminergic+AntiMuscarinic = AntiEmetic/AntiNauseaDoxylamine (Promethazine) Adrenoreceptor Blocker: Promethazine Serotonin Blocker: Cyproheptadine Wide Distribution Greater CNS entry Duration of action: 4-6 hours (Meclizine: 12-24 hours) Block Autonomic Receptors Reversible Competitive Antagonism H1 Selectivity Rapid Acting No AntiCholinergic effects Absence of Sedation
Unsuitable for daytime use, car driving, machinery workers psychomotor performance (AntiHistamine H1) CNS: alertness & concentration, motor incoordination, fatigue Promethazine: Adrenoreceptor BlockerOrthostatic hypotension, reflex tachycardia AntiHistamine/AntiSerotonin: Appetite AntiMuscarinic: Dry Mouth, Altered Bowel & Bladder, Vision Blurring
Second generation
Narrow Spectrum of Uses: Allergic rhinitis (hay fever) Conjunctivitis Urticaria, atopic eczema
Additional AntiAllergic mechanisms: Inhibit cytotoxic mediator release, Eosinophil Chemotaxis, inhibit platelet activating factors CNS entry Metabolized by CYP3A4Drug Interactions Long Acting: 12-24 hours Active Metabolites of Drugs available: Loratidine-Desloaratidine Cetrizine-Lovocetrizine Terfenadine-Fexofenadine Reversible Competitive Antagonism
Pointes) due to blockage of IKr (HERG) potassium channels responsible for repolarization of heart +CNS depressants: additive effect Autonomic blockade of older Antihistamines are additive w/ AntiMuscarinics Terfenadine, Astmezol banned-vent arrhythmia-TdP No role in Asthma: Asthma due to Leukotriene & PAF Low concentration at site of action No role in other humoral & cell mediated allergies
Adrenalin e
Anaphylaxis/Anaphylactic Shock Caused by Histamine, Leukotriene, Prostaglandin Administer: Adrenaline Followed by- AntiHistamine: Chlorpheneramine Glucocorticoids: Hydrocortisone BP, Bronchodilation, Laryngeal edema release of mediators
Class Nitrates
Drug Short acting: Glyceryl Dinitrate, isosrbide dinitrate ( sublingual) Long acting: oral, transdermal
blocker
Phenylalkylamine : Verapamil
Benzothiazepines: Diltiazem
MYOCARDIAL INFARCTION/ANTI-ANGINAL Site/Mechanism Uses ADR Angina Pectoris Throbbing headache Venodilationpreload NSTEMI Tolerance Arteriolar Hypertensive dependance dilationTPRAfterload emergency Coronary dilation LV failure Abdominal Colic Cyanide Poisoning Anti-adrenergic Classical & Unstable TG angina CO/cardiac work and quality of life MI myocardial O2 requirements Worsening Peripheral Mild CHF reninangiotensin vascular disease Hypertension CHF Arrythmia Heart block Dissecting Aortic Tiredness & reduced Aneurysm exercise Hypertrophic obstructive cardiomyopathy Migraine, thyrotoxicosis, Anxiety, tremors, glaucoma Ca2+ CCB: interfere w/ Cardiac arrhythmia channel Ca2+ entry in the Migraine, nocturnal blockcellblood vessel leg cramp NERVE cell relaxationCO SA,AV node Block L type SMOOTH & voltage channel Angina pectoris Weak uterine contraction, CARDIAC Hypertension foetal hypoxia, muscle Premature labor tachycardia, hypotension Hypertrophic placental perfusion cardiomyopathy, Reynauds disease Broad Cardiac arrhythmia spectrum: Angina pectoris nerve + Hypertension muscle Hypertrophic cardiomyopathy Visceral+vascular smooth muscle dilation Arterial+veno dilation Dilation of epicardial & deeper vessels coronary blood flow Nitrate + CCB Nitrate - preload CCB - afterload Hypertension MI-nicorandilcardioprotective
+verapamil/diltiazem=SA & AV nodal depressioncardiac arrestdeath +insulin & oral antidiabeticsdelay recovery from hypoglycaemia Blocks warning symptoms of hypoglycaemia: tremors, seating, tachycardia + agonists (cold remedies: ephedirine/phenylephrine)=BP (unopposed action) +NSAIDS= blocker effect Propanolol=lignocaine metabolism
+blockercardiac depression-death
+blockercardiac depression-death
K+ channel openers
Nicorandil Pinacidil
Combinations
Nitrate- x blocker cardiac dilation & blood flow Aspirin: 162-325 mg-chewed &swallowed Nitroglycerine: sublingual0.4mg/5min O2 Morphine
Vasospastic angina
coronary blood flow blocker - cardiac work Anti-thrombotic therapy: Antiplatelets: clopidogrel (ADP), abciximab (Gp 2b/3a), Apirin (COX) Anticoagulant: heparin/enoxaparin Anti-ischemic/Cadioprotective therapy: Cardioselective blockers, ACE inhibitors, Nitrates PCI: first preference Favored after 3 hrs w/in 90 mins-door to balloon angioplasty/stent placement Fibrinolytics: w/in 30 mins- door to needle after 6 hrs- poor efficacy Prevention of Recurrence: Aspirin: lifelong blockers: metoprolol2 years ACE inhibitors Antihyperlipidemics: statins Thrombolytic: rTPA-alteplase-STEMI <6hrs of onset mortality/preserve LV function Aspirin: antiplatelet-irreversibly acetylating COX cardiovascular events mortality following AMI Morphine: opioid-analgesic anxiety, cardiac metabolic demands sympathetic activity Nitrates: coronary vasodilation coronary blood flow ventricular load-venodilation blockers: Atenolol, Metoprolol cardiac work & O2 demandinjury & death & infarct size- myocardial salvation Maintain coronary flow to subendocardium acute mortality, prevent recurrence automaticity: delay in AV conduction/cardioprotective sudden ventricular fibrillation ACEI: w/in 24 hr6 weeks Reverses remodeling caused by Ang2 early & long term mortality Clopidogrel, unfractionated heparin(PCI)
In hospital management
Complete bed rest Aspirin & Heparin: after fibrinolysis(x reocclusion) blocker: w/in 24 hrs2 years ACE inhibitors: STEMI-w/in 24 hrs Antihyperlipidemic drugs
Mechanism rate of conduction in tissue w/ fast potential Ignores slow potential - SA, AV nodes
ANTI-ARRHYTHMICS Effects AP duration & refractoriness conduction through ventricle Repolarization rate QRS & QT intervals AP duration and refractoriness conduction through ventricles Repolarization rate automaticity in ectopic foci conduction in all cardiac tissues Slow gradual Ca2+ influxautomaticity blocker: Ca2+ influx PR interval; no change in QRS
Uses
ADRs/Interactions/Contraindications myocardial contractility, cardiac arrest +diureticshypokalemiatorsades de Pointes GIT side effects Hypersenstivity Neurological: dizziness, drowsiness, nausea, blurred vision, paraesthesia, confusion, convulsion Bradycardia Hypotension
Class 2 blocker
Phase 4
Phase 3
receptorsattached to Ca2+ channels blocker: Ca2+ influx similar to class 4 (CCB) K+ effluxprolongs repolarization & ERP
Atrio-ventricular re-entrant tachycardia Supraventricular arrhythmias associated w/ exercise, emotion & stress Sinus tachycardia Extrasystoles
GI symptoms, blurred vision, tremors Contraindicated-Sick sinus syndrome, heart failure, MI Severe bradycardia cardiac contractility, cardiac arrest
Amiodarone
Phase 2 (Phase 4)
Verapamil Diltiazem
Adenosine ( 1 agonist)
Digoxin
SA/AV automaticity AV nodal conductivity ERP PR interval Breaks reentrant circuit Hyperpolarization of membrane conduction velocity via slow potential/Ca2+ channels No effect on fast potential/Na+ channel PR interval Inhibits Na/K ATPase of myocardial fibers intracellular Na+ intracellular Ca2+ (via
Supraventricular and Ventricular arrhythmia Resistant ventricular tachycardia Recurrent ventricular fibrillation Atrial fibrillation: maintain sinus rhythm Paroxysmal Supraventricular Tachycardias (PSVT) Poor efficiency in ventricular arrythmia Paroxysmal Supraventricular Tachycardias (PSVT) involving AV node-alternative to verapamil
Bradycardia, Heart block Hypothyroidism: amiodarone has Iodine GI related Photosenstivity Skin & corneal pigmentation Peripheral neuropathy Pulmonary alveolitis & fibrosis (serious) Hypotension, Bradycardia Additive AV block Negative inotropic effect
Na/Ca exchange pump) contractility & excitability of contracting cells generation & propagation of impulse in SA & AV conduction velocity PR interval, depresses ST segment Enhance Vagal activity: INDIRECTLY
ANTI-HYPERLIPIDEMICS Action Endogenous Class Statins Drug Simvastatin(PrD) Atorvastatin(LnAct) Rosuvastatin(LnAct) Lovastatin(PrD) Mechanism Hmg CoA red Hepatic Cholesterol synthesis LDL receptors on hepatocytes plasma LDL clearance PPAR- Lipopritien Lipase Synthesis clearance of VLDL and Chylomicrons Actions Total Cholesterol LDL TG HDL Adverse Myopathy Hepatitis-serum transaminase GI disturbance Rash, Insomnia, Angioedema Rash, Nausea, Dyspepsia, Diarrhea, Myopathy testosteroneimpotence liver enzymes Flushing & pruritus GI disturbance Hepatotoxicity Hyperuricemia Impaired glucose tolerance Therapeutic Contraindications/ Interactions
TG HDL
Hepatic & Renal Disease Pregnancy & lactation oral anticoagulants Myopathy
Nicotinic Acid
Adipose:Binds to NA recptors-FFA mobilization-TG & VLDL synthesis Liver:Inhibits DAG acyltransferase-2 (key TG synthesis enzyme)-VLDL synthesis Plasma:Lipoprotein Lipase activityclearance of VLDL & chylomicrons Ezetimibe (oral) Interferes with cholesterol transport protein NPC1L1 (intestine) cholesterol absorption
Exogenous
Bind to Bile acidLDL interrupt NE TG enterohepatic circulation excretion of bile in feces cholesterolbile hepatic cholesterol-LDL receptor on hepatocytesclearance of LDL Statins Fibrates Ezetimibe Fibrates Nicotinic Acid
Constipation, Hypercholesterolemia Delasy absorption Flatuence Patients who cannot of Warfarin, Impaired fat soluble tolerate other drugs Digoxin, vit absorption Chlorothiazide gallstones
LDL
TG
Features
ANTI-HYPERTENSIVES Effects
Uses
ADR
Interactions/Contraindi cations
angiotensin bradykinin
ARB
Competitive antagonist of AT-1 receptor Block L-type channels Arteriolar vasodilation coronary tone myocardial O2 requirements LV wall stress HR Smooth Muscle Relaxation: Bronchiole, Uterine, GIT Afterload only
No reflex sympathetic stimulation BP:TPR, angiotensin II, vasoconstriction, aldosterone Vasodilation (bradykinin) Renal:vasodilation, protienuria, no electrolyte disturbance No Cough (bradykinin metabolized)
Hypertension, CHF: TPR first line MI: reduce mortality Diabetic nephropathy Progressive renal impairment: ESRD, protienuria, Systemic resistance
Hypotension (CHF w/ diuretics) Hyperkalemia (renal pts) Cough (bradykinin) Teratogenic ARF (bilateral renal artery stenosis)
Verapamil
Diltiazem
AV nodal conduction: in Supraventricular Reentry tachycardia Atrial fibrillation-ventricular response Sympathetic blockade Typical Angina Atrial tachycardia/flutter/fibrillation Migraine AV nodal conduction: in Supraventricular Reentry tachycardia Atrial fibrillation-ventricular response Sympathetic blockade Typical Angina Variant Angina Atrial tachycardia/flutter/fibrillation Less effect on AV nodal conduction Typical Angina Variant Angina Hypertension Pregnancy induced Hypertension
Dihydropyridi ne
Reflex Sympathetic Stimulation: Reflex Tachycardia, BP swing MORTALITY in CAD MI risk in hypertensive Vasodilation: flushing, headache, ankle edema, BP Elderly: Urine retention Can be used in overt heart failure
Direct Vasodilator s
TPRBPRefle x sympatheticsco ntractility, HR, O2 consumpMI, angina, Heart failure (counteract: blocker) Reninsalt&H2 O retention (counteract: diuretic)
TPRdiast olic BP Forms NO IV: T1/2 is small (2-5 min) continuous infusion TPR&COs ys & dias BP
Arteries & Arterioles Arteries & Veins BP Reflex tachycardia Preload & Afterload
Lupus Syndrome MetabolismCN _ ion Large dose: Toxicity+thiosul phateThiocynat ekidneys excrete Light sensitive: protect from light
K channel opener IV Long acting (624 hrs) plasma & ECF volumeCOB Pgradual in TPR Sympathetic depressant HR, inotropy & COBP cardiac work & O2 consumption
Arteriole
Hypertensive Emergencies
Diuretics
blockers
Cardiac Glycosides
Drugs Source/Comment Digoxin: Foxgrove Plant Fast acting (15Sugar Steroid 30 mins) Lactone ring Commonly used protein binding T1/2: 40 hrs Digitoxin: Slow onset Not commonly used protein bound T1/2: 5-7 days
CONGESTIVE HEART FAILURE Mechanism Effects Inhibits NA/K ATPaseI/C contractionventric NaNa/Ca pumpCa ular efflux &CA influx ejectionEDV&ESV CO: Sympathetic, HR, TPR Renal perfusion, Edema SA:rate Atria:refractory period AV:conduction velocity refractory period Purkinje/Ventricle: refractory period (slight) ECG: PR,QT interval venous tone Kidney: diuresis
Uses Heart failure CHF + Atrial fibrillation Severe/Chronic CHF + LV systolic dysfunction Atrial flutter/fibrillation: Av node conduction AV node ERP
ADRs & Antidote Initial: GIT: Anorexia Nausea, Vomiting Diarrhea CNS: Elderly-disorientation & hallucinations Color vision disturbance Antidote: Lower dose Cardiac: Delayed afterdepolarizations Ventricles: Bigeminy Fibrillation/tachycardia Heart block ECG: PVB, inverted T wave, depressed ST segment; tachycardia, fibrillation, arrest SA: rate Atria: refractory periodarrhythmias AV node: refractory periodarrhythmias Purkinje/Ventricles: Extrasystoles, tachycardia, fibrillations K+: Mild: skip 1-2 doses; oral K+ supplementation <5 meq/L Severe/Suicidal: K+ levels; not give K+ supplements Suicide/severe poisoning: Digoxin antibodiesFab fragments bind & inactivate drug Arrhythmias: Antiarrhythmic- lidocaine, phenytoin
Interactions + K+: digoxin binding to Na/K ATPase +hypokalemia due to steroids/diuretics : toxicity
+ Ca2+: Hypercalcemia, toxicity + other drugs: qunidine, amiodarone, tetracycline toxicity due to digitalis concentration
1 agonists
Dobutamine
Arrythmias Tachycardi a
cellmyofibrilscontractio n force PDE are enzymes that inactivate cAMP & cGMP PDE inhibitors: X PDEcAMP & cGMP Non selective vasodilator: Arteries & Veins X ACE (kininase 2) angiotensin 2sympathetic activityVasodilationafte rload aldosteronesalt & water retentionvenous returnpreload
dopamine BP Inotropic agent Vasodilation Acute Heart Failure, raise BP Severe Heart Failure
Vasodilators
ACE inhibitors
Enalapril Lisinopril
Non selective vasodilator: CHF: Arteries & Veins First line afterload & preload ventricular dilation long term remodeling efficacy of diuretic treatment mortality & morbidity Asymptomatic patients w/ LV dysfunction + no edema Symptomatic patients: preload and afterload Hypertension MI Diabetic Nephropathy ACEI intoleration due to cough CHF: all stages Hypertension Dyspnea NOT FIRST LINE Patients w/ DRUGS Isosorbide increased dinitrate + fatigue Antihypert hydralazin erem ensiveodelling pregnancy + methyl (africans) DOPA CHF Hypertensive emergency CHF: FIRST LINE Furosemide/loop diuretic: Acute pulmonary edema, severe chronic failure Spirinolactone: Severe chronic heart failure, morbidity &mortality
Mortality Nausea, Vomiting Arrhythmias Liver enzyme Thrombocytopenia First dose hypotension (post diuretics) Cough (bradykinin) Hyperkalemia Dysguesia, rashes, urticarial Acute Renal Failure; angioedema TERATOGENIC
No cough
Block AT-1 receptor (angiotensin-2 receptor) No effect on ACEBradykinin metabolized Venodilator preload Arteriole dilator
Sodium Nitroprusside Diuretics Loop diuretics Furosemide Bumetanide Torsemide Chlorothiazide Hydrochlorothia zide Spirinolactone Eplerenone
NOcGMP
Hypokalemia: leads to digoxin interaction Hypervolemia Ototoxicity Hyperuricemia: Gout Metabolic alkalosis Hyperlipidemia
blockers
Start w/ low doses mortality in stable severe heart failure EF,HR, symptoms Long term: death rate, symptoms, sense of well being, better clinical status
Neseritidine Bosentan survival in CHF ACEI, ARB, blockers, spirinoloactone, hydralazine+nitr ate
BNP, IV continuous infusion Endothelin receptor antagonist Stage A: High risk, No symptoms Risk factors Treat: hypertension, hyperlipidemia, diabetes, obesity (ACEI/ARB for vascular disease)
work, Na & H20 ACEI or ARB Thiazide diuretic blocker (in stable class 2-4) Digitalis (if systolic dysfunction/atri al fibrillation) Nitrate/hydralaz ine (vasodilator) Cardiac resynchronizati on (if wide QRS)
Acute Heart Failure Can be due to AMI Anemia, fevermetab olic demand exertion, emotion, Na
Stage B: Structural disease, No symptoms Risk factors Treat: hypertension, hyperlipidemia, diabetes, obesity (ACEI/ARB, blockers)
Stage C: Structural disease, Symptoms Na, H20, Work Diuretics, ACEI, ARB Digitalis: systolic dysfunction + 3 HS/atrial fibrillation blockers ( in stable class 2-4) Spirinolactone Stage D: Refractory Symptoms Na, H20, Work Diuretics, ACEI, ARB Digitalis: systolic dysfunction + 3 HS/atrial fibrillation blockers ( in stable class 2-4) Spirinolactone Cardiac resynchronization Cardiac transplant
SHOCK Type of Shock Hypovolemic/Oligemic shock Low Volume Mechanism Internal & external fluid losspreload Hemorrhagic/Non Hemorrhagic Trauma Non traumatic: Vaginal, GI, GU Burns, Diarrhea Vomiting Diuresis, Sweating Third Space Loss: Pancreatic, peritonitis, bowel obstruction Cervical spinal cord injury/severe head injuryloss of sympathetic vasomotor tonearteriolar & venodilationpooling of blood in post capillary capacitance blood vesselpooling of venous systemvenous return & cardiac output Severe LV dysfunctionsystemic hypoperfusion MI, acute myocarditis Treatment Volume resuscitation: rapid infusion-isotonic saline, ringers lactate NaHCO3-correct acidosis Inotropic support following volume support-Dobutamine, Dopamine O2 Acute hemorrhage/anemia: Whole Blood & plasma Absence of Blood & plasma: Colloidal plasma expanders Human albumin, Dextran, Hydroxyethylstarch Crystalloid plasma substitute: superior to colloids-Normal saline, 5% dextrose, ringer lactate Penylephruine/Norepinephrinevascular resistanceMAP IV fluids for relative hypovolemia
Septic/Bacteremic/Endotoxic shock
Anaphylactic shock
MI: Morphine,O2, nitroglycerine, aspirin, alteplase (fibrinolytic), metoprolol ( blocker), captopril (ACEI), heparin (anticoagulant) Dopamine: Low dose-dilates renal vascular bed Moderate dose- +ve chronotropic & inotropic effects Dobutamine: +ve chronotropic & inotropic effects IV fluids: maintains adequate blood volume Infection treatment, Hemodynamic & Respiratory support w/in 1hr of presentation Antimicrobial: Empirical: effective against both GN & GP microorganism After microbial culture: appropriate antimicrobial treatment Remove focal source of infection NaHCO3-corrects acidosis Vasopressor-for hypotension O2 Recombinant activated protein C: Sepsis associated w/ excess inflammatory response & altered coagulation & fibrinolysis Anti-inflammatory & Anti-apoptotic Septic shock w/ adrenal insufficiency: Glucocorticoids (hydrocortisone 100 mg IV TID) Adrenaline: 0.5 mg of 1:1000 IM reversal of hypotension, bronchospasm, laryngeal edema IV fluids Hydrocortisone hemisuccinate: 100mg IV/IM- inhibit late phase of allergic reaction Chlorpheneramine: 10-20 mg slow IV O2, assisted ventilation Norepinephrine 1, 2, 1 Strong vasoconstrictionBP Shock w/ severe hypotension
Dopamine D1, D2, 1, 1 Low dose: 2 g/Kg/minD1dilates renal vascular bed Moderate dose: 2-10 g/Kg/minD1,1+ve chronotropic & inotropic effect
Dobutamine 1 selective inotropic w/ afterload reduction(peripheral vasodilator)minimize cardiac O2 consumption Cardiogenic shock-pump failure due to MI
Neurogenic shock
Vasopressin: Catecholamine resistant shock Milrinone: PDE inhibitor Potent inotrope & chronotrope Shock treatment: Early recognition ABC resuscitation Fluid restoration Vasopressors (AFTER fluid restoration) Restore O2 delivery Control inciting pathological process Maintain vital organ function
Hypovolemic shock Volume replacement Dopamine Dobutamine YES Endotoxic shock YES Cardiogenic shock NO Anaphylactic shock
POSSIBLY
YES POSSIBLY
YES YES
YES YES
POSSIBLY NO
Adrenaline
NO
NO
NO
YES
Glucocorticoids
NO
YES
NO
YES
Antihistaminics
NO
NO
NO
YES
HEMATINICS Oral Fe Ferrous Sulphate (32%) Ferrous Fumarate (33%) Ferrous Gluconate (12%) Colloidal Ferric Hydroxide (50%) Preferred Ferrous>Ferric absorption Empty stomach Upper intestineabsorbed ADRs Epigastric pain Nausea, vomiting, heartburn Metallic taste Staining of Teeth Bloating ADRs Local: Pain Skin Pigmentation Sterile abscess Systemic: Fever, headache, joint pain, flushing Palpitation, chest pain, dyspnea LN enlargement Anaphylaxis Renal DiseaseX Fe sorbitol
Iron Sorbitiol-Citrate IM
Fe overload
MW MW IM(locally bound)/IV IM-Not locally bound Not excreted 30 % excreted Absorbed through Absorbed through Lymphatics Circulation Not transferrin bound Transferrin bound Taken up by macrophagesslowly Directly available available to erythron Normal-2.5-3mg >7 mgtissue damage Acute Fe Poisoning: >60mg/Kg Vomiting, Abdominal Pain, Hematemesis Diarrhea, Lethargy Cyanosis, Dehydration, Acidosis Convulsions Shock, CVS collapse
IM-deep gluteal injection Z technique-avoid skin staining 2ml-daily/alternate days 5 ml each side on same day IV-0.5 ml Fe Dextran after test dose over 5-10 min Infusion-diluted in 500 ml glucose/saline Fe sorbitol-not iv
USES Fe deficiency anemia (treatment & prophylaxis) Megaloblastic anemia FeCl3-astringent in throat pain
B12/Cobalamin deficiency: Gastric failure: Pernicious anemia Total gasterectomy Ileal failure: Crohns disease: regional enteritis Ileal resection Tropical sprue Competing organism: Bacterial overgrowth (blind loop) Diphyllobothrium latum
Folate deficiency: Folate poor diet: Alcoholism, poverty Folate requirement: Pregnancy Severe hemolytic anemia Severe psoriasis Drug therapy Tropical sprue
Management: Prevent further Absorption: Induce vomiting/gastric lavage Oral egg yolk & milkcomplex iron Activated charcoal useless Bind & remove absorbed Fe: Chelating Agent: Desferroxamine DTPA/Ca edetate BAL contraindicated Supportive Measures: Correct fluid/electrolyte balance CVS support Convulsions: Diazepam Clinical features: B12 & Folate: Megaloblastic anemia Fatigue, weight loss, fundal hemorrhage, diarrhea, fever, sore tongue, appetite loss, jaundice B12 deficiency: Paraesthesia, neuropathy, dementia, demyelination of spinal cord Pernicious anemia: Family & personal history of vitiligo, Autoimmune thyroid disease
Hemopoetic GF Erythropoetin: peritubular cells of kidneyRBC MCSF, GCSFWBC Thrombopoetinplatelets Stem cell factor IL
Treatment: Transfuse (care) B12-oral or parenteral Folate tablets Severe cases: hypokalemia
Epoetin: r Human Erthropoetin Uses: Chronic Renal Failure Cancer Chemotherapy AIDS anemia Premature infants Dose: 25-100 IU/Kg/SC IV 3x a Wk Adverse Flu like symptoms Mild Hypertension Encephalopathy Thrombosis Fe & Folate demand
Causative Drugs/Causes Antimalarials: Primaquine Chloroquine Fansidar Maloprim Sulfonamides: Sulfacetamide Co-trimexazole Dapsone Antibiotics: Chloramphenicol Furazolidone Niridazole Nalidixic acid Nitrofurantoin Antidiabetics: Glibenclamide Analgesics; High dose ASPIRIN Vitamin K analogues Naphthalene Penicillin-High Dose: Ab against drug-RBC complex Quinidine Rifampin: Drug-ag-ab deposits complement on RBC surface Methyldopa Fludarabine
DRUGS AFFECTING BLOOD ELEMENTS Treatment/Therapeutic Drugs Stop drug Treat underlying infections Severe anemiablood transfusion Hemoglobinuriamaintain good renal flowavert renal damage Neonatal jaundicephototherapy
Adverse effects
Chemical AgentsHemolysis
Dapsone-High Dose
Stop Drug CORTICOSTEROIDS: PrednisoneFIRST LINE Azathioprine, Cyclosporin, Cyclophosphamideused when other measures fail Splenectomy Severe Cases: Blood Transfusions Folate Stop Drug Severe Anemia: Blood Transfusion
Thalassemia
Regular Blood Transfusion Folate-regular use Splenectomy: 6yrs+ Hepatitis B vaccine Allogenic BM transplant
Iron OverLoad: Liver damage Endocrine: growth failure, delayed/absent puberty, DM, hypothyroidism, hypoparathyroidism Myocardium Siderosis Iron Chelator: Parenteral: Desferoxamine 1-2g IV or 20-40 mg/Kg SC w/ each unit of blood
Adverse : Rapid IV: hypotension Idiosyncratic reactions: Flush, Rash Pulmonary, Neurosensory toxicity Oral: Defipirone, Deferasirox Endocrine therapy: GH, insulin, Ca, Vitamin D Aplastic Anemia Chemicals: Benzene, DDT, insecticides, Hair Dye Drugs: Anticancer: Busulphan Cyclophosphamide Anthracyclines Nitrosoureas Idiosyncratic: Chloramphenicol Sulphonamide Gold General Treatment: Stop Drug/Chemical Anemia: Blood transfusions, Platelet concentrates Infections: Prevent & Treat-cultures, Broad spectrum prophylactic antibiotics, antifungals, GCSF Severe Thrombocytopenia Fibrinolytic Inhibitors: Tranexamic Acid or Aminocaproic Acid Platelet transfusion Allogenic Stem Cell Transplantation Specific Treatment: Anti Lymphocyte Globulin (ALG) & Anti Thymocyte Globulin (ATG): cytotoxic T cells Adverse: Fever & Chills: Prednisolone Serum Sickness: spiking fever, arthralgia, skin rashes Cyclosporin: primary treatment + ATG + steroids Combination Immunotherapy: ATG (4 days) + cyclosporine (6 months) + Methylprednisolone (2 weeks) Hemopoetic Growth Factors Stem Cell Transplantation General Treatment: Stop Drug Prevent & Treat infections: Bacterial Usually Can also be: Viral, Fungal, Protozoal Specific Treatment: GCSF GM-CSF Autoimmune Neutropenia: Corticosteroids & Splenectomy Rituximab: Anti CD-20 (Monoclonal Antibody)
Neutropenia
Anticancer Drugs: Alkylating agents-non selective neutropenia Antibiotics: Chloramphenicols Sulfonamides Co-trimexazole Cephalosporins Antipsychotics: Chlozapine Chlorpromazine Antithyroids: Carbimazole Anti-Inflammatory: Phenylbutazone Gold Salts Anti-Epileptic: Phenytoin Carbamazepine
Thrombocytopenia
Penicillamine Ticlopidine Bone Marrow Suppression: Anticancer, Ethanol Chloramphenicol, Co-trimoxozole, Arsenic Immune: Analgesics, Anti-inflammatory: Gold Salts Antibiotics: penicillin, trimethopterin, sulfonamides Antiepileptic: Diazepam, Carbamazepine Diuretics: Acetazolamide, Furosemide Antidiabetics: Chlorpropamide Digoxin, Heparin, Methyldopa, Quinidine Platelet Aggregation: Heparin Myeloid Growth Factor: rG-CSF: Filgrastim neutrophils rGM-CSF: Sargramostim neutorphils, eosinophils, monocytes Uses: Post chemotherapy, radiotherapy, autologous SC transplant Peripheral mobilization of SC for autologous SC transplant (G-CSF) Severe neutropenia, Aplastic anemia
Erythropoetin: Hb, Erythropoesis, circulatory reticulocytes EPOETIN , DARBOPOETIN : IV, SC Uses: Anemia due to CRF/AIDS, cancer/drugs Anemia in premature babies Pre-Operationto blood transfusions Adverse: Thrombosis, BP
General Treatment: Blood Transfusion/Platelet Concentrates Specific Treatment: Corticosteroids: Prednisolone (High Dose) Splenectomy: Patients w/ steroid failure or in need of high dose steroids Immunoglobulin: Rituximab (anti CD 20); high dose modify autoAb production Immunosuppression: Azathioprine, Cyclosporin, Cyclophosphamide when other measures fail Megakaryocyte Growth Factor: OPRELVEKIN (IL 11) Megakaryocyte Growth Factor: Oprelvekin: IL-11 Thrombopoetin Uses: Thrombocytopenia /after cancer therapy Adverse Effects: Fatigue, Headache, Dizziness, Fluid Retention CVS effects: Dilutional anemia, dyspnea, Transient Atrial Arrythmia
ANTI-PARASITIC Disease Antimalarial Class Erythrocitic Schizonticide Drug Chloroquine Mechanism Degradation of RBC HB Fast & Long Acting Uses Prophylaxis & Cure of ALL types of Malaria Infectious Mononucleosis Rheumatoid Arthritis Multidrug Resistant Plasmodium falciparum malaria Multidrug Resistant malaria Cerebral malaria + Tetracycline=effect Nocturnal muscle cramps, varicose veins, myasthenia gravis P. falciparumcurative Toxoplasmosisfirst choice Adverse Effects toxicity; side effects GIT-A/N/V, epigastric pain CVS: IV; BP; arrhythmia CNS: toxicity Eye: retinal damage Ear: Hearing Defects Not Parenteral Avoid in cerebral/complicate malaria Resistance effective, toxicity than chloroquine Highly toxic8-10 g-fatal Cinchonism: CTZ damage, vomiting, tinnitus Hemolysis PregnancyAbortion
Mefloquine
Quinine
Sulfonamide Slow and Long (sulfamethopyrazine/sulfadoxine)+Pyremethamine acting (S/P) Erythrocytic phase of P. falciparum Antifolate (like Cotrimoxazole) Tetracyclines Weak & Slow acting
SulfonamideSerious toxicityExfoliative dermatitis, Steven Johnson syndrome Not prophylactic Single Dose
Blood Schizonticide
Halofantrine
Artemesinin Derivatives Artisunate: Water SolubleOral, IV, IM Artemether: Lipid Soluble Arteether: IM
Primaquine
Fastest and Short acting Prodrugs Damage ER & Protein synthesis in parasites Kills falciparum gametes Effective against Gametocytes & Hypnozoites Selectively
All Plasmodium species +Quinine or S/PChloroquine resistant Falciparum Doxycycline (100 mg/day): Second Line ProphylacticChloroquine resistant Falciparum malaria Multidrug Resistant P. falciparum P. vivax Used when other drugs not working Multidrug Resistant Falciparum malaria treatment
Leishmaniasis
Sodium Stibogluconate
Trypanosomiasis
Pentamidine
sensitize microfilariae for phagocytosis Inhibits SH dependant enzymes of parasite Inhibits topoisomerase 2 & aerobic glycolysis
Fever, Rash LN enlargement N/V, abdominal pain Pancreatitis Kidney & Liver Damage Highly Toxic Strong alkaline naturereleases Histamineanaphylaxis Heart, Liver, Kidney damage
Trypanosoma cruzi Nifurtimox/Benznidazole-Acute disease Trypanosom Early disease: IV suramin gambiense/rhodensiense Late disease + CNS involvement: suramin + melarsoprol (crosses BBB) + corticosteroids (prevents reactive encephalopathy) Toxoplasmosis Sulfadiazine + Pyrimethamine +Falinic acid (prevents BM suppression) Causal Prophylaxis: Suppressive Prophylaxis: Clinical cure: terminate episode of malarial fever Pre/exo-erythrocytic Erythrocytic Phase Erythrocytic Schizonticides phasecause of malaria suppressionprevents Fast acting High efficacy: used alone Prevent clinical attacks malarial fever Chloroquine, Mefloquine, Quinine, Amodiaquine, Proguanil: P. falciparum Clinical symptoms Halofantrine, Lumefantrine, Artemesinine, Primaquine: all malarial suppressed; Atovaquone. species exoerythrocytic phase Slow acting Low efficacy: used in combination not affected Proguanil, Sulfonamides, Pyrimethamine, Chloroquine: Tetracycline 300mgx2tabs/wk; 1wk before & 1 month after endemic area return Radical Cure: total eradication of parasite from Resistant cases: body Proguanil 200 mg daily + Exo-Erythrocytic drugs + Erythrocytic drugs = total Chloroquine 300 mg cure weekly P. falciparum & P. malariae: clinical Mefloquine 250 mg cure=erythrocytic schizonticides=erythrocytic weekly-4wks after parasite elimination is enough. No exoerythrocytic endemic area return phase Doxycycline 100 mg 1day P. vivax & P. ovale: Relapsing before to 4 weeks after malariaerythrocytic & exoerythrocytic/hypnotic endemic area return parasite elimination Exo-Erythrocytic drugs + Erythrocytic drugs Falciparum Malaria: Multi Drug Resistant Vivax Malaria: Chloroquine sensitive: Falciparum Malaria: Chloroquine sensitive: Chloroquine + Primaquine Uncomplicated Acute Chloroquine + Primaquine (gametocidal) Multidrug Resistant Chloroquine Resistant: Chloroquine resistant: Falciparum Malaria: Quinine + Doxycycline + Primaquine -Artesunate ACT-Artemesinine based +Sulfadoxine+pyrimethamine Combination Therapy (S/P)+Primaquine Artemesinine + -Artesunate + Mefloquine Erythrocytic
Trypanosomiasis Leishmaniasis AIDS patients: Pneumocystis jiroveci pneumonia Chagas disease Sleeping sickness
Gametocidal Elimination of male & female gametes from patients blood Not beneficial to patient; Reduces transmission to mosquito Primaquines & Artemesinines: Gametocidal to all species Chloroquine & Quinine: Vivax gametes
Congenital/disseminated disease Antimalarial Classification: 4-aminoquinolines: Chloroquine Quinoline Methanol: Mefloquine Cinchona Alkaloid: Quinine Biguanides: Proguanil Diaminopyridine: Pyrimethamine 8-aminoquinolines: Primaquine Sulfonamides: Sulfadoxine, Sulfamethopyrazine Tetracycline Sasquiterpine Lactone: Artesunate, Atemether, Arteether Amino Alcohol: Halofantrine Mannich Base: Pyronaridine Naphthoquinone: Atovaquone Most Antimalarials: Hemolysis in G6PD deficiency
Prevention Of Malaria in Travelers: ChloroquineAreas w/o resistant P. falciparum Malarone=Atovaquone+ProguanilAreas w/ chloroquine resistant P. falciparum (WHO) MefloquineAreas w/ chloroquine resistant P. falciparum DoxycyclineAreas w/ multidrug resistant P. falciparum PrimaquineTerminal Prophylaxis of P. vivax & P. Ovale
-Artemeether + Lumefantrine -Quinine + Doxycycline Cerebral malaria: Chloroquine sensitive malaria drugs IV
Schizonticide
Stavudine Didanosine
Mechanism Deoxythymidine Analog AZTThymidine KinaseTriphosphate form Competitive Inhibition of dTTP for Reverse Transcriptase Enzyme Causes Chain Termination Thymidine Analog Synthetic Deoxyadenosine Analog
ANTIRETROVIRALS Uses Adverse Effects IV & Oral Myelosuppression: Neutropenia, Anemia HIV 1, HIV 2, HTLV GI intolerance: N/V Headaches, Insomnia HIV treatment: progression & Crosses BBB survival Metabolite in urine Prevents Mother to Child HIV transmission Peripheral Neuropathy Lipidystrophy Pancreatitis Peripheral Neuropathy D/N/V Abdominal Pain Peripheral Neuropathy N/V Headache Fatal Hypersensitivity Prevents HIV transmission from mother to neonate at labor/delivery TERATOGENIC
Zalcitabine
Cytosine Analog
Delavirdine Efavirenz
Protease Inhibitors
Cytosine Analog Guanosine Analog More effective Binds to Viral Reverse TranscriptaseRNA & DNA dependent DNA polymerase blockade Substrate & Inhibitors of CYP3A4 Do not compete w/ nucleoside triphosphates Do not require Phosphorylation Protease: Cleaves large precursor polyprotein moleculefunctional componenets Inhibit Protease (late step in replication) prevent spread of infection
Lipidystrophy: Abdominal Obesity, Buffalo Hump, Limb & Face wasting Dyslipidemia GI intolerance Dizziness Numbness Rashes Headache Limb & Facial tingling Asthenia Hyperlipidemia Insulin resistance
Fusion/Entry Inhibitor
Enfuvirtide (T-20)
Binds to gp-41 subunit of viral glycoprotein envelopeprevents conformational changes required for fusion of viral & cellular membranes Blocks FusionPrevents entry into/infection of CD 4 cells
Integrase Inhibitor
Raltegravir
Anti HIV regimens: Zidovidine + Lamuvudine + Lopnavir (PI) Zidovidine + Lamuvudine + Efavirenz (NNRTI)
Post Exposure Prophylaxis: Low Risk: Zidovidine (300 mg) + Lamuvidine (150 mg) 2xdaily for 4 weeks High Risk: + Indinavir (800 mg) 3xdaily for 4 weeks
Drug Streptokinase
THROBOLYTICS, ANTITHROMBOTICS AND COAGULANTS Description Action Uses Non enzymatic AMI: Thrombolytic Therapy-w/in 6 protein hrs of symptoms hemolytic Peripheral Arterial Thrombosis streptococci Catheter & Shunt patency Proactivator PE + Hemodynamic Instability plasminogen Severe DVT complexcatalyzes Acute Ischaemic Stroke: rTPA w/in 3 formation of hrs of symptoms plasmin Peripheral Vascular Disease
ADR Action blocked by Antistreptococcal Ab 1Year should be elapsed before next use Allergy, Hypotensiongenerating Kinins
Contraindications Absolute Contraindications: Neurosurgery/Head trauma <2 mts Severe Active Bleeding/ Internal Hemorrhage Cerebrovascular Hemorrhage <6 mts Cerebral tumor/aneurysm Relative Contraindications: Recent Major Trauma Invasive Surgery < 10 days GI/genitourinary bleeding Recent CardioPulmonary Resuscitation Peptic Ulcer <3 mts Pregnancy Uncontrolled Hypertension Thrombocytopenia
Urokinase
Enzyme-Human urine Cultured Human Renal CellsNonAntigenic Potent Direct Plasminogen Activator rDNA technology Expensive
Non Antigenic
Anistreplase
Anisoyloted Plasminogen Streptokinase Activator Complex (APSAC) Complex: Purified Human Plasminogen + Bacterial Streptokinase Sulfated Mucopolysaccharide IV/SC Not given IMhematoma formation Immediate onset 4-6hrs Monitor: aPTT = 2-2.5 control
Better than streptokinase & urokinase in dissolving older clots Does not act on circulating plasminogen Non Antigenic Rapid action Clot selectivity Activity on plasminogen associated clots than free blood plasminogen Thrombolytic Activity HeparinActivates Anti Thrombin 3 (AT-3)Inhibits Factors 2a (Thrombin), 9a, 10a Bleeding time Clotting time aPTT Inhibits Coagulation InVivo & InVitro Inhibits Aldosterone Secretion
DVT & PE: Prophylaxis-for bed rest, high risk surgeries, CancerLow dose UFH, LMWH, Fondaparinaux Treatment-UFH, LMWH for 5-6 days, then Warfarin for 3-6 mts Pregnant Women-
Bleeding: risk: careful patient selection, Dosage control, monitor aPTT Heparin Induced Thrombocytopenia (HIT): Ab formed to Heparin & Platelet Specific Protien - Platelet Factor 4 (PF4) Systemic hypercoagulable state Leads to Venous Thrombosis Perform platelet count frequently
Drug hypersensitivity, HIT Active Bleeding/Risk,Intracranial Haemorrhage, Active TB, Hemophillia, TTP, Recent SurgeryCNS, eye, postate Threatened Abortion Brain & Spinal Cord Injury Anaesthesia: Regional & Lumbar block Severe Hepatic & Renal Impairment
Heparin-SC Atrial Fibrillation w/ emboliztion Artificial Heart Valves, PC angioplasty Cardiac bypass: Aspirin, Heparin Rheumatic Heart Disease DIC: Heparin Acute Unstable Angina: Aspirin 160 mg/day + Heparin, followed by Warfarin PE, DVT HIT AMI
Treatment: Direct Thrombin Inhibitor, Fondaparinaux Allergy: Animal Origin-asthma, urticaria Therapy-Transient Alopecia Osteoporosis: >6 mts use
Low Molecular Weight Heparins (LPWH): Enoxaparin Dalteparin Tinzaparin MW: 3000-7000
Heparin Fragments
Inhibits Factor 10a Less effect on Thrombin (2a) Equally efficacious as UFH No effect on CT, aPTTNo lab test required SCBioavailability Long T1/2Less frequent dosing1/2 weekly Bleeding, HIT Anti Thrombin 3 mediated selective inhibition of Factor 10a No effect on Thrombin (2a) SC Long T1/2: 15 hrs Directly bind to active site of Thrombin
Fondaparinaux
Hirudin/Lepirudin Hirudin: Leech Saliva (Bivalent DTI) Lepirudin: Specific recombinant form irreversible Thrombin Inhibitor Bivalirudin (Bivalent DTI) Argatroban (Univalent DTI)
HIT Anaphylaxis
Coronary Angioplasty HIT Coronary Angioplasty in HIT patients Inhibits Vit K EpoxideVit K Hydroquinone (active form) Inhibits synthesis of Vit K dependent Factors 2,7,9,10 (TENS) Bleeding: Common-Haematuria, Epistaxis, Bleeding Gums, Uterine, Intracranial Ulcer-FATAL Treatment: Vitamin K (antagonist), Fresh Blood/Plasma Infusion Teratogenic: Fetal Warfarin Syndrome- Fetal Hemorrhage, Abnormal Bone Formation
Inhibits Vit K EpoxideVit K Hydroquinone (active form) Inhibits synthesis of Vit K dependent Factors 2,7,9,10 (TENS)
Potentiating Factors (anticoadulation) -bleeding -Hepatic Disease: synthesis of clotting factors -Fever & Thyrotoxicosis: metabolism (destruction) of clotting factors -Malnourishment, Malabsorption, New Borns: Vitamin K Inhibiting Factors (coagulation) -Thrombosis -Pregnancy: synthesis of Clotting factors -Hypothyroidism: metabolism (destruction) of clotting factors -Genetic warfarin resistance
Slow Complete Absorption Delayed onset: (1-3 days) plasma protein binding Crosses Placenta & Secreted in Milk Metabolized in Liver Dose Regulation: Monitor PT-reduce to 25% of control INR Full effect: 4-5 days even if INR reaches therapeutic level in 1-2 days PK: Enzyme Induction & Inhibition, PP binding PD: Synergismimpaired hemostasis/clotting factor synthesis (hepatic disease), Competitive antagonism-Vit K, Hereditary resistance to oral anti coagulants
Necrosis: Thrombosis in Venules-Soft Tissues-Breast & Buttocks Warfarin Sodium: Alopecia, Urticaria, Severe Dermatitis +Rifampicin&Barbiturates (metabolism), Vitamin K(clotting factors)Thrombosis +Phenylbutazone&Aspirin(platelet aggr), Cimetidine, Metrinidazole, Erythromicin, Cotrimoxazole, fluconazole (metabolism)Potentiate
Phenindione Dabigtaran
Hypersenstivity No routine INR monitoring required Fewer Drug Interactions compared to Warfarin Prevent Stroke & Thromboe mbolism in Atrial Fibrillation Prevent Blood Clotting in Test Tubes
In Vitro
AntiPlatelet
Ethylene Diamine Tetra Acetic Acid (EDTA) Citrate Lithium Heparin Prostaglandin Synthesis Aspirin Inhibitors
Calcium Chelators
Inhibits COX & Thromboxane Synthase Irreversibly TXA2 synthesis in Platelets Bleeding Time in
Clopidogrel Ticlopidine
vivo Low Dose: 75-100 mg Platelets exposed to aspirincannot synthesize new enzyme Blocks ADP Receptor (P2Y12) ADPplatelet aggregation ADP-RBinhibits aggregation
Active MI & IHD Primary & Tertiary prevention of MI post MI Aspirin Intolerant Patient Transient Ischemic Attacks Stroke, Unstable Angina Coronary Stent PCI AMI/Acute Coronary Syndromes Prevent stroke in cerebrovascular disease & transient ischemic attacks Patency of implanted bypass in CABG: Aspirin + Abciximab Nausea, Diarrhea, Leukopenia Thrombocytopenic Purpura Clopidogrel: Less ADR, Safer
Abciximab
Chimeric Monoclonal Antibody against Gp 2b/3a receptor Occupies ReceptorInhibits Ligand Binding Inhibits Platelet PDE enzyme cAMPPGI2 Weak effect on Platelet Aggregation Platelet Inhibition Better Than Clopidogrel Platelet Inhibition Direct Inhibitor of ADP Receptor (P2Y12) Reversible
Prasugrel
Platelet Inhibition
+Aspirincereb rovascular ischemia +WarfarinArtif icial Heart Valves ischemic events Thrombolysis in AMI
Oral, reversible
Treat Overdosage of Fibrinolytics Hemophilics: Limit excessive bleeding after Surgery Prevent recurrence of SubArachinoid Hemorrhage Abruptio Placenta, Post-Partum hemorrhage, Menorrhagia Oral 7 x more potent than ACA CABG Surgery: Blood Loss Heparin Antagonist Basic Protien Fish Sperm Slow IV 1 mg Protamine Sulphate for every Heparin Antagonist Combines w/ Heparin as an ion pairStable complex devoid of anticoagulant
Coagulants
Vitamin K
Deficiency due to: Liver Disease, Malabsorption Syndromes, long term antibiotic use Deficiency Symptoms: Bleeding: Urine, Nose, GIT, SkinEcchymoses
Plasma Fractions
Factor 8 Anti-Hemophilic Factor Prothrombin Complex Concentrates Factor 9 Complex Factor 7a Cryoprecipitate Fibrinogen
Treat Hemophilia A
Liver Disease, Blood Loss Factor 7 deficiency Hemophilia A Liver Disease DIC
Megaloblastic Anemia:
Hb: RBC: WBC: =/ Platelet: =/ Reticulocyte: Hct: MCV: MCH: =/ MCHC: = Serum LDH: Serum Bilirubin: B12 &/or Folate: B12<100pg/ml PBS: hypersegmented neutrophils, macroovalocytes BM: erythroid hyperplasia Penicious Anemia: Serum Ab to parietal cells Serum Ab to IF Achlorydia (HCl ve)
Aplastic anemia: Congenital: Fanconi Secondary: Radiation, Chemical, Drugs: Chloramphenicol, Infections: Parvovirus B19, HIV, Hep A, B, C DD: Severe Megaloblastic anemia w/ pancytopenia MDS Primary Myelofibrosis Marrow Fibrosis secondary to any other disease
Hb: RBC: WBC: Platelet: PBS BM: Trephine-dry tap w/ hypocellular imprints Fanconi: Kidney & Spleen hypoplasia Hypoplasia of bone: Thumbs/radii Short stature
PRCA: Congenital: Diamond Blackfan AcquiredPrimary-AI destruction of erythroid precursors Secondary: -Thymic tumorthymoma -Malignancy-CLL, lymphoma -drugs, pregnancy -AI-SLE -Virus: Parvovirus B19, EB
Myelophthisic anemia; Space occupying lesions: Marrow infiltration: metastatic tumor, granuloma Marrow Fibrosis: Primary, Secondary to hemmatopoetic malignancies
Anemia of Chronic Disease: Normocytic Normochromic/Mildly microcytic, hypochromic MCV: 77-82;rarely<75 Hb rarely<9 Reticulocytopenia Serum Fe TIBC Serum Ferritin: =/ BM Fe store: Perls stain: = Hepcidin: caused by IL1 & TNF
Iron Deficiency Anemia: Microcytic Hypochromic MCV: MCH: Hb: RBC: Serum Fe: TIBC:
Hereditary Spherocytosis: AD Hb: Reticulocytosis: 520% PBS: spherocytes DAT: normal Osmotic Fragility:
Malaria
Sexual: Gametogony: Mosquito Sporogony: humans Asexual: Schizogony: humans Sporozoites liver schizonts (hypnozoites) blood RBC trophozoites Schizonts (merozoites) or gametocytes mosquito gut ookinete oocysts sporozoites Oocystcat ingests tachyzoitestissue bradyzoites/oocysts
Anemia, cyclic fevermerozoites lyse RBC & get released Cerebral Malaria: falciparum-aggregates of RBCs occlude capillaries Relapse: hypnozoites- Vivax Ovale
Toxoplasma gondii
Trypanosoma cruzii
Leishmania donovanii
Infective: Ocysts from cat feces/raw meat transplacental Reduviid Bug Infective: Trypomastigotes Diagnostic: Trypomastigotes/ Amastigotes Tsetse Fly-both sexes Infective: metacyclic trypiomastigotes Gambiense: west Diagnostic: Africa-Human trypomastigotes Rhodensie: east Africa-Animalantelope SandflyInfective: Phlebotomus, Promastigotes Lutzomyia Diagnostic: Amastigotes Animal: Dog, small carnivores, rodents Human: India Reservoir: Forest rodents
Trophozoites: Brain, eye, Liver Tissue Cysts-enlarge & cause symptoms Encephalitis in AIDS patients: impaired CMI Myocarditis: amastigotes kill myocytes Neuronal Damage: Megacolon, Megaoesophagus
Blood meal Trypomastigotes Reduviid Bug Midgut: Epimastigotes Hind gut: Trypomastigotes defecated human amastigotes trypomastigotes Blood meal Trypomastigotes Midgut: epimastigotes (procyclic) salivary glands: trypomastigotes (metacyclic) Blood stream
Blood Meal Amastigotes Midgut: promastigotes Migrate to pharynx/proboscis human: macrophages Amastigotes