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RECEPTORSReceptor Class Mechanism/Second
messengerSite Action Effect Drug receptor
selectivityα α1 ↑DAG & IP3↑ IC Ca2+ Blood Vessel Smooth Muscle-TPR
(skin)Pupil Radial muscleIntestine, Prostate, Bladder sphincter
Vasoconstriction-Blood vessels-TPRMydriasis↓GIT, Contraction-↓urinary
VASOCONSTRICTION ↑BP on stimulation/agonistMydriasis-good in glaucoma
Epinephrine>Norepinephrine>>>>>>>>>Isoproterenol
α2 ↓cAMP↓Norepinephrine release
Presynaptic receptor↓Nor(auto)/Ach(hetero)INHIBITORYPancreatic β cell↓insulinFat, Platelet
↓Nor/Ach—Neuromodulation—inhibitory↓insulin & lipolysis (DOMINANT)Platelet aggregation
↑blood sugar on stimulation↓ insulin release
β β1 Heart↑Ino, Chrono, AV nodal conduction velocityJG cells↑Renin
↑BP, ↑HR,↑conduction↑Renin↑fluid retention↑venous return↑SVCO↑BP;↑Ang2↑TPR↑afterload↑heart work,↑BPGIT smooth muscle relaxation
↑BP on stimulation/agonist Isoproterenol>Epinephrine>Norepinephrine
β2 Blood Vessel SKELETAL, (coronary)Uterine Smooth muscleRespiratoryLiverPancreatic β cellCiliary muscle
VasodilationRelaxation (tocolysis)BronchodilationGlycogenolysis↑insulin (MILD)Relaxation-Mydriasis
↑blood flow to skeletal muscle/HEART↑ air in lungs↑ energyGood in glaucoma On stimulation/agonist
Isoproterenol>Epinephrine>>>>>>>>>>Norepinephrine
β3 Fat cell ↑lipolysisDopamine D1 type-
D1, D2↑cAMP:↑adenylyl cyclase Blood vessel-Smooth muscle:
Renal, Splanchnic, CORONARY, Cerebral--RELAXATION
Vasodilation↑blood flow (CORONARY)
D2 type-D3, D4, D5
↓ adenylyl cyclaseOpen K channel↓Ca influx
Nerve terminal ↓Norepinephrine releaseAutoregulator
Cholinergic Nicotinic Agonist-small dose Nicotine Antagonist-Large dose nicotine Ach↓Norepinephrine at vasoconstrictor nervesAchM3NO/EDRF releasevasodilation (cavernous muscle-erection) Sildenafril
Skin of face, Neck, salivary glandsstimulate/agonistblushing
Cholinergic drug-all vessels dilate
Muscarinic Agonist-Muscarine Antagonist-Atropine
Histamine H1 Smooth Muscle-intestine, airwayEndotheliumBrain
Smooth Muscle ContractionBlood Vessel: (Short Lasting) Vasodilation-NO, PG releasecapillary permeability, gap junction wideningSmooth muscle: vasoconstriction-larger vesselsAfferent Nerve Stimulation
BronchoconstrictionAllergies
Sensory Nerve Endings-stimulation-painWaking AmineTriple response-ID injectionRed spot, edema & flareBP(vasodilation), sense of warmth, Headache
H2 Gastric Parietal CellsCardiac MuscleSmooth MuscleBrain
Gastric Gland-Gastric Acid SecretionBlood Vessels: (persistent) Vasodilation-smaller vesselsHeart: +ve Chronotropy & +ve Inotropy, HR
Peptic Ulcer
H3 Histaminergic NeuronsMyenteric Plexus
Presynaptic H3 Receptors-release several transmitters
AGONISTSClassification Drug Class Receptors Action Effect Uses ADR/Interactions
DIRECTLY ACTING Epinephrine Catecholamines Allα1=α2;β1=β2
Low dose-β action-vasodilationHigh dose-α action-vasoconstriction
β2-dilates coronaries & skeletal blood vessels-↑blood flowα1&2-consticts blood vessels of skin & mucosa
ANAPHYLACTIC SHOCK(α)(IM), local anaesthetic, GLAUCOMA(α1), local bleed (nose)(α 1&2)Physiological antagonist of HistamineGlauomaHeart block, cardiac arrestLocal hemostasis(α1)
+COCAINE↑CVS effects
↑cardiac work-ischaemia, MI, heart failure↑BP↑HRArrythmiasPulmonary edema
Norepinephrine α1=α2β1>>>β2α1,α2,β1 agonist
α1 –vasoconstriction-↓TPR-↑BP
↑BP ShockDopamine preferred
↑BP*baroreceptor*VagusREFLEX BRADYCARDIA (α1)
Isoproterenol β1=β2>>>>αMainly β;Less α
Heart block, cardiac arrest
Dopamine D1=D2>>β1>>α
D1, α, β1 agonist
Low dose:D1-vasodilation-renal, splanchnic↑blood to kidney, visceraD2-presynaptic autoreceptor-↓Norepinephrine releaseModerate dose: (D1)↑contraction,conduction (heart)High dose: α-vasoconstriction
Inotrope Cardiogenic/Septic shockInotrope-↑CO, xHR↑perfusion kidney, viscera↑urine outputAcute HF
Xylometazoline, Oxymetazoline, Naphazoline Pseudoephederine,
α Vasoconstriction of nasal mucosaTopical-long acting
Nasal decongestants
Initial sting↑BPProlong: Atrophic rhinitis
Selective Adrenergics Phenylephrine Selective α1 agonist
α1 VasoconstrictionMydriasis
Nasal DecongestantMydriasis-retinal examGLAUCOMA
No cycloplegia ↑BP
Methoxamine Selective α1 agonist
Clonidine Selectiveα2 agonist
α2Central sypatholytics
↓vasomotor sympathetic center↓BP, relax peripheral blood vessels
Antihypertensive↓TPR-relax peripheral blood vessels
AntihypertensiveGLAUCOMA-apraclonidie
Withdrawal reaction of Opiates, Benzodiazepines
αmethylDOPA Selectiveα2 agonistαmethyl analogue of DOPA (precursor of DA, NE)
Antihypertensive-synthetic-no ADR/interactionGLAUCOMA
No ADR/interaction therefore Coombs test/DAT globulin negative
Dobutamine Selective(relatively) β1 agonist
β1>β2>>>α
↑intropy, conduction--↑CONo ↑ in O2 demandx HR, BP, TPR
Inotrope Cardiogenic/Septic/Renal shockCHF-inotropePost MI shock/pump failureCardiac surgery
Sinus tachycardia, Arrhythmia
Salbutamol, Terbutaline
Selective β2 agonist
β2 Brochodilation Asthma Skeletal muscle tremors
Isoxurine, ritodrine Uterine relaxation
Premature labor
MIXED ACTION Ephederine Mixed acting adrenergic
Direct α+β actionAlso indirect action
Release Norepinephrine + α&β stimulation
Long actingLess efficacy
Postural HypostensionMa Huang-weight loss, appetite suppression
↑CNS: tremors, anxiety, insomnia, convulsions, anorexia
Pseudoephederine Mixed acting adrenergic
Nasal decongestant
Mephentermine α & β agonist
INDIRECTLY ACTING
↑Release Amphetamines:Dex/Met Amp, Modafinil, Methylphenidate
Indiectly acting adrenergic
↑Norepinephrine release
↑CNS, alertness↓weight
Modafinil-EpilepsyMethyphenidate: ADHD
Drug of Abuse↑CNS: tremors, anxiety, insomnia, convulsions, anorexia
Tyramine Indiectly acting adrenergic
↑Norepinephrine release
Present in fermented food- cheese, wine, sausagesMetabolized: Liver-MAO enzyme
↓Reuptake Cocaine Indirectly acting adrenergic
↓Reuptake at noradrenergic synapses
Drug of Abuse: ↑Dopamine in brain neurons
ANTAGONISTSType Class Drug Uses/effect Action ADR/Interactions
α blocker Nonselective PhenoxybenzamineErgotamineDihydroergotaminePhentolamineChlorpromazine
Phentolamine:Penile erection for impotence
α1 blockade↓TPR↓CO↓BP
Secondary shock-reflex vasoconstriction-hypovolemic shockCHF-short term reliefPeripheral vascular disease
Postural hypostension-dizziness & syncopeNasal stuffiness-dilated blood vessels-extravasationMiosis-cholinergic-pupillae constrictorDiarrhea: cholinergic dominanceInhibition of ejaculation
Selective
α1 blocker Prazosin HypertensionPheochromocytoma
Tamsulosin BPHTerazosine
α2 blocker Yohimbineβ blocker Propanolol Hypertension ↓vasodilation-β2 blockade
↓Renin-↓Ang2-↓TPR-↓BP-β1 blockadeHeart β1 blockade-↓CO-↓BP
Anticholinergic M3: vascular endothelial cell
Atropine No marked effect on BP Normal dose-Blocks Ach agonist-↓vasodepressor action (↓TPR; INDIRECT)Large dose: Direct Vasodilator
Anti Histamin
ergic
H1 Blocker
First generation DipenhydrinateDipenhydramineHydroxineCyclizineMeclizineCinnarazineChlorpheneraminePromethazineCyproheptadine
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, Promethazine- tremor,rigidity(Anti Chloinergic)
Pregnancy Nausea/Vomiting: Doxylamine, Promethazine
Motion Sickness: Dipenhydramine/inate, Promethazine, Cyclizine, MeclizinePomethazine:
Vestibular Disturbances: Cinnarazine (AntiHistaminic, AntiCholinergic, Anti5HT)
AntiAllergic-(Histamine=type 1 S)
SedativeHighly: Dipenhydramine/inate, PromethazineModerately: Pheniramine, Cyproheptadine, Meclizine, Cinnarazine
Anticholinergic:Dipenhydramine/inate, Promethazine
AntiHistaminergic+AntiMuscarinic = AntiEmetic/AntiNausea-Doxylamine (Promethazine)
Adrenoreceptor Blocker: Promethazine
Serotonin Blocker: Cyproheptadine
Wide DistributionGreater CNS entryDuration of action: 4-6 hours(Meclizine: 12-24 hours)
Unsuitable for daytime use, car driving, machinery workers psychomotor performance(AntiHistamine H1)
CNS: alertness & concentration, motor incoordination, fatigue
Promethazine: Adrenoreceptor Blocker-Orthostatic hypotension, reflex tachycardia
AntiHistamine/AntiSerotonin: Appetite
AntiMuscarinic: Dry Mouth, Altered Bowel & Bladder, Vision Blurring
Block Autonomic ReceptorsReversible Competitive Antagonism
Second generation FexofenadineLoratidine, DesloratidineCetrizine, LevocetrizineAzelastineEbastine
Narrow Spectrum of Uses:Allergic rhinitis (hay fever)ConjunctivitisUrticaria, atopic eczemaAcute Allergic reactions to Drugs & Food
H1 SelectivityRapid ActingNo AntiCholinergic effectsAbsence of SedationAdditional AntiAllergic mechanisms:Inhibit cytotoxic mediator release, Eosinophil Chemotaxis,inhibit platelet activating factorsCNS entryMetabolized by CYP3A4Drug InteractionsLong Acting: 12-24 hoursActive Metabolites of Drugs available:Loratidine-DesloaratidineCetrizine-LovocetrizineTerfenadine-Fexofenadine
Reversible Competitive Antagonism
Terfenadine/astemezol + CYP3A4 inhibitors (ketoconazole/erythromycin/itraconazole)-Ventricular Arrhythmias (Torsades de 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
Adrenaline
Physiologic antagonist of Histamine
Anaphylaxis/Anaphylactic ShockCaused by Histamine, Leukotriene, ProstaglandinAdminister:AdrenalineFollowed by- AntiHistamine: ChlorpheneramineGlucocorticoids: HydrocortisoneBP, Bronchodilation, Laryngeal edema release of mediators
No role in Asthma:Asthma due to Leukotriene & PAFLow concentration at site of action
No role in other humoral & cell mediated allergies
MYOCARDIAL INFARCTION/ANTI-ANGINALClass Drug Site/Mechanism Uses ADR Interaction
Nitrates Short acting: Glyceryl Dinitrate, isosrbide dinitrate ( sublingual)Long acting: oral, transdermal
VenodilationpreloadArteriolar dilationTPRAfterloadCoronary dilation
Angina PectorisNSTEMIHypertensive emergencyLV failureAbdominal ColicCyanide Poisoning
Throbbing headacheTolerancedependance
+sildenafil/Viagra=death+other antihypertensives=BP
β blocker Anti-adrenergicCO/cardiac work and myocardial O2 requirementsreninangiotensin
Classical & Unstable anginaMIMild CHFHypertensionArrythmiaDissecting Aortic AneurysmHypertrophic obstructive cardiomyopathyMigraine, thyrotoxicosis, Anxiety, tremors, glaucoma
TGquality of lifeWorsening Peripheral vascular diseaseCHFHeart blockTiredness & reduced exercise
+verapamil/diltiazem=SA & AV nodal depressioncardiac arrestdeath+insulin & oral antidiabeticsdelay recovery from hypoglycaemiaBlocks warning symptoms of hypoglycaemia: tremors, seating, tachycardia+α agonists (cold remedies: ephedirine/phenylephrine)=BP (unopposed action)+NSAIDS=β blocker effectPropanolol=lignocaine metabolism
Calcium Channel Blockers
Phenylalkylamine : Verapamil
Ca2+ channel block-NERVE cell – SA,AV node
CCB: interfere w/ Ca2+ entry in the cellblood vessel relaxation↓COBlock L type voltage channel
Cardiac arrhythmiaMigraine, nocturnal leg cramp
+βblockercardiac depression-death
Dihydropyridine: Nifedipine, Amlodipine, Lercanidipine
SMOOTH & CARDIAC muscle
Angina pectorisHypertensionPremature laborHypertrophic cardiomyopathy, Reynaud’s disease
Weak uterine contraction, foetal hypoxia, tachycardia, hypotension↓placental perfusion
Nifedipine: tachycardia & death
Benzothiazepines: Diltiazem
Broad spectrum: nerve + muscle
Cardiac arrhythmiaAngina pectorisHypertensionHypertrophic cardiomyopathy
+βblockercardiac depression-death
K+ channel openers
NicorandilPinacidil
Visceral+vascular smooth muscle dilation
HypertensionMI-nicorandil-
Arterial+veno dilationDilation of epicardial & deeper vessels↑coronary blood flow
cardioprotective
Combinations β blocker + Long acting nitrate
Nitrate + CCB β blocker + nitrate + CCB
AVOID verapamil+ diltiazem
βblocker-x nitrate tachycardiaNitrate- x β blocker cardiac dilation & ↓blood flow
Nitrate - ↓ preloadCCB - ↓ afterloadVasospastic angina
Nitrate - ↓preloadCCB - ↓afterload + ↑coronary blood flowβ blocker - ↓ cardiac work
Pre-hosptal/Emergency management
Aspirin: 162-325 mg-chewed &swallowedNitroglycerine: sublingual-0.4mg/5minO2Morphine
NSTEMI:Stabilize acute coronary lesionRx residual ischemiaProphylaxis
Anti-thrombotic therapy:Antiplatelets: clopidogrel (ADP), abciximab (Gp 2b/3a), Apirin (COX)Anticoagulant: heparin/enoxaparinAnti-ischemic/Cadioprotective therapy: Cardioselective β blockers, ACE inhibitors, Nitrates
Prevention of Recurrence:Aspirin: lifelongβ blockers: metoprolol2 yearsACE inhibitorsAntihyperlipidemics: statins
Thrombolytic: rTPA-alteplase-STEMI<6hrs of onset↓mortality/preserve LV functionAspirin: antiplatelet-irreversibly acetylating COX↓cardiovascular events↓mortality following AMIMorphine: opioid-analgesic↓anxiety, cardiac metabolic demands↓sympathetic activityNitrates: coronary vasodilation↑coronary blood flow↓ventricular load-venodilationβ blockers: Atenolol, Metoprolol↓cardiac work & O2 demand↓injury & death & infarct size- myocardial salvationMaintain coronary flow to subendocardium↓acute mortality, prevent recurrence↓automaticity: delay in AV conduction/cardioprotective↓sudden ventricular fibrillationACEI: w/in 24 hr6 weeksReverses remodeling caused by Ang2↓early & long term mortalityClopidogrel, unfractionated heparin(PCI)
In hospital management
Complete bed restAspirin & Heparin: after fibrinolysis(x reocclusion)β blocker: w/in 24 hrs2 yearsACE inhibitors: STEMI-w/in 24 hrsAntihyperlipidemic drugs
STEMI:Reperfusion therapy
PCI: first preferenceFavored after 3 hrsw/in 90 mins-door to balloonangioplasty/stent placementFibrinolytics:w/in 30 mins- door to needleafter 6 hrs- poor efficacy
ANTI-ARRHYTHMICSClass Phase of
actionMechanism Drugs Effects Uses ADRs/Interactions/Contraindications
Class 1Na channel blocker
Phase 0Phase 4(Phase 0 & 3)
↓rate of conduction in tissue w/ fast potentialIgnores slow potential - SA, AV nodes
1aQuinidineProcainimide(phase 0 & 3)
↑AP duration & refractoriness↓conduction through ventricle↓Repolarization rate↑ QRS & QT intervals
Atrial & Ventricular arrythmias ↓myocardial contractility, cardiac arrest+diureticshypokalemiatorsades de PointesGIT side effectsHypersenstivity
1bLidocaineMexiletine(phase 3)
↓AP duration and refractoriness↓conduction through ventricles↓Repolarization rate↓automaticity in ectopic foci
Ventricular arrythmiasIneffective in atrial arrythmias
Neurological: dizziness, drowsiness, nausea, blurred vision, paraesthesia, confusion, convulsionBradycardiaHypotension
1cFlecainide(phase 0)
↓conduction in all cardiac tissues
Atrio-ventricular re-entrant tachycardia
GI symptoms, blurred vision, tremorsContraindicated-Sick sinus syndrome, heart failure, MI
Class 2β blocker
Phase 4 β receptors-attached to Ca2+ channelsβ blocker: ↓ Ca2+ influx similar to class 4 (CCB)
PropanololEsmolol (short acting)
Slow gradual Ca2+ influxautomaticityβ blocker: ↓ Ca2+ influx↑PR interval; no change in QRS
Supraventricular arrhythmias associated w/ exercise, emotion & stressSinus tachycardiaExtrasystoles
Severe bradycardia↓cardiac contractility, cardiac arrest
Class 3K+ channel blocker
Phase 3 ↓K+ effluxprolongs repolarization & ERP
Amiodarone ↓ K+ efflux↑Repolarization & ERP↑PR, QRS, QT interval
Supraventricular and Ventricular arrhythmiaResistant ventricular tachycardiaRecurrent ventricular fibrillationAtrial fibrillation: maintain sinus rhythm
Bradycardia, Heart blockHypothyroidism: amiodarone has IodineGI relatedPhotosenstivitySkin & corneal pigmentationPeripheral neuropathyPulmonary alveolitis & fibrosis (serious)
Class 4Ca2+ channel blocker
Phase 2(Phase 4)
Similar effect as β blocker
VerapamilDiltiazem
↓SA/AV automaticity↑AV nodal conductivity↑ERP↑PR intervalBreaks reentrant circuit
Paroxysmal Supraventricular Tachycardias (PSVT)Poor efficiency in ventricular arrythmia
Hypotension, BradycardiaAdditive AV blockNegative inotropic effect
Adenosine (α 1 agonist)
Very short acting purine nucleotide
Hyperpolarization of membrane↓conduction velocity via slow potential/Ca2+
Paroxysmal Supraventricular Tachycardias (PSVT) involving AV node-alternative to verapamil
Transient dyspnea, Chest pain↓BPVentricular standstill or fibrillation
channelsNo effect on fast potential/Na+ channel↑PR interval
Digoxin Na/K ATPase inhibitor
Inhibits Na/K ATPase of myocardial fibers ↑intracellular Na+↑intracellular Ca2+ (via Na/Ca exchange pump)↑contractility & excitability of contracting cells↓generation & propagation of impulse in SA & AV conduction velocity↑PR interval, depresses ST segmentEnhance Vagal activity: INDIRECTLY
Paroxysmal Supraventricular Tachycardia (PSVT)Atrial flutter/fibrillation
GI relatedDisturbances in color visionAtrial ArrhythmiaGynaecomastia, hyperkalemia
ANTI-HYPERLIPIDEMICS
Action Class Drug Mechanism Actions Adverse Therapeutic Contraindications/Interactions
Endogenous Statins Simvastatin(PrD)Atorvastatin(LnAct)Rosuvastatin(LnAct)
Lovastatin(PrD)
↓Hmg CoA red↓Hepatic Cholesterol synthesis↑LDL receptors on hepatocytes↑plasma LDL clearance
↓Total Cholesterol↓LDL↓TG↑HDL
MyopathyHepatitis-↑serum transaminaseGI disturbanceRash, Insomnia, Angioedema
HypercholestrolemiaIIa, IIb
Anticoagulants & Antidiabetics95% PP bindingTERATOGENIC
Fibric Acid Derivatives
GemfibrozilBezafibrateClofibrate
Fenofibrate
PPAR-α↑Lipopritien Lipase Synthesis↑clearance of VLDL and Chylomicrons
↓TG↑HDL
Rash, Nausea, Dyspepsia, Diarrhea, Myopathy↓testosterone-impotence↑liver enzymes
HyperTGemiaIIb, III, IV, V
Hepatic & Renal DiseasePregnancy & lactation↑oral anticoagulants↑Myopathy
Nicotinic Acid Adipose:Binds to NA recptors-↓FFA mobilization-↓TG & VLDL synthesisLiver:Inhibits DAG acyltransferase-2 (key TG synthesis enzyme)-↓VLDL synthesisPlasma:↑Lipoprotein Lipase activity-↑clearance of VLDL & chylomicrons
↓VLDL(hepatic secretion)↓LDL↓TG (synthesis)↓FFA (from adipose tissue)↑HDL
Flushing & pruritusGI disturbanceHepatotoxicityHyperuricemiaImpaired glucose tolerance
↑HDLHyperTGemia
IIb, V
Exogenous Cholesterol Uptake Inhibitors
Ezetimibe (oral) Interferes with cholesterol transport protein NPC1L1 (intestine) - ↓cholesterol absorption
Diarrhea , Headache, Myalgia
HypercholestrolemiaCombined with
statins-synergisticIIa
Bile Acid Binding Cholestyramine Bind to Bile acid- ↓LDL Constipation, Hypercholesterolemia Delasy absorption
Resins ColestipolColesevelam (no dug
interaction)
interrupt enterohepatic circulation↑excretion of bile in feces↑cholesterolbile↓hepatic cholesterol-↑LDL receptor on hepatocytes-↑clearance of LDL
NE TG FlatuenceImpaired fat soluble vit absorption↑gallstones
Patients who cannot tolerate other drugs
of Warfarin, Digoxin, Chlorothiazide
↑ LDL StatinsFibrates
Ezetimibe
↑ TG FibratesNicotinic Acid
ANTI-HYPERTENSIVES
Class Drugs Mechanism Features Effects Uses ADR Interactions/Contraindications
Renin inhibitors
β blockersAliskrenin (oral unapproved)
Inhibit rennin secretion
ACE inhibitors
Enalapril, Captopril, Benazepril
Inhibit ACEno Angiotensin II
↓angiotensin↑bradykinin
No reflex sympathetic stimulation↓BP:↓TPR, ↓angiotensin II, ↓vasoconstriction, ↓aldosterone↑Vasodilation (bradykinin)Renal:↑vasodilation, ↓protienuria, no electrolyte disturbance
Hypertension, CHF: ↓TPR first lineMI: reduce mortalityDiabetic nephropathyProgressive renal impairment: ↓ESRD, ↓protienuria, ↓Systemic resistance
Hypotension (CHF w/ diuretics)Hyperkalemia (renal pts)Cough (↑bradykinin)TeratogenicARF (bilateral renal artery stenosis)
+NSAID:↓PG synthesis, ↓vasodilation+K sparing diuretic (spironolactone):↑K
ARB Losartan, Valsartan, Irbesartan
Competitive antagonist of AT-1 receptor
Inhibit angiotensin IINo effect on bradykinin
No Cough (bradykinin metabolized)
Hypertension w/ cough (ACEI) Hypotension , Hyperkalemia,Teratogenic
Calcium Channel Blockers
Verapamil Block L-type channelsArteriolar vasodilation↓coronary tone↓myocardial O2 requirements↓LV wall stress↓HRSmooth Muscle Relaxation: Bronchiole, Uterine, GIT↓Afterload only
Cardiac>vascular smooth muscle
↓AV nodal conduction:in Supraventricular Reentry tachycardiaAtrial fibrillation-↓ventricular responseSympathetic blockadeTypical AnginaAtrial tachycardia/flutter/fibrillationMigraine
↓Ca2+ influx in heartCardiac depression/arrest/failure↓HRAV block
AV conduction abnormalitiesOvert Heart Failure
Verapamil/Diltiazem + β blockerAV block↓ventricular function
Diltiazem Cardiac=vascular smooth muscle↓inotropy vs Verapamil
↓AV nodal conduction:in Supraventricular Reentry tachycardiaAtrial fibrillation-↓ventricular responseSympathetic blockadeTypical AnginaVariant AnginaAtrial tachycardia/flutter/fibrillation
↓Ca2+ influx in heartCardiac depression/arrest/failure↓HRAV blockConstipation
Dihydropyridine
Nifedipine1 genShort acting
Reflex Sympathetic Stimulation:Reflex Tachycardia, BP swingMORTALITY in CAD
Cardiac<vascular smooth muscle
Less effect on AV nodal conductionTypical AnginaVariant AnginaHypertensionPregnancy induced Hypertension
Reflex Sympathetic Stimulation:Reflex Tachycardia, BP swingMORTALITY in CAD↑MI risk in hypertensiveVasodilation: flushing, headache, ankle edema, ↓BPElderly: Urine retention
Unstable Angina: ↑ risk of adverse cardiac events
Amlodipine2 genHR, CO not affected
Can be used in overt heart failure
Direct Hyadralazine/dihydralazine ↓TP ↓TP Arteries & Arterioles Moderate Hypertension Lupus Syndrome ↓BP
Vasodilators
R↓BPReflex sympathetics↑contractility, HR, O2 consump↑MI, angina, Heart failure(counteract: β blocker)↑Renin↑salt&H2O retention(counteract: diuretic)
R↓diastolic BP
Pregnancy Induced Hypertension Palpitation↑HR, AnginaFluid retentionEdema
Sodium NitroprussideForms NO
Forms NOIV: T1/2 is small (2-5 min) continuous infusion↓TPR&CO↓sys & dias BP
Arteries & Veins↓BPReflex tachycardia↓Preload & Afterload
Hypertensive Emergencies MetabolismCN_ ionLarge dose: Toxicity+thiosulphateThiocynatekidneys excreteLight sensitive: protect from light
DizoxideK channel opener
K channel openerIVLong acting (6-24 hrs)
Arteriole Hypertensive Emergencies
Diuretics ↓plasma & ECF volume↓CO↓BPgradual ↓ in TPR
β blockers Sympathetic depressant↓HR, inotropy & CO↓BP↓cardiac work & O2 consumption
CONGESTIVE HEART FAILUREClass Drugs Source/Comment Mechanism Effects Uses ADRs & Antidote Interactions
Positive Inotrope
Cardiac Glycosides
Digoxin:Fast acting (15-30 mins)Commonly used↓protein bindingT1/2: 40 hrsDigitoxin:Slow onsetNot commonly used↑protein boundT1/2: 5-7 days
Foxgrove PlantSugar SteroidLactone ring
Inhibits NA/K ATPase↑I/C NaNa/Ca pump↓↓Ca efflux &↑CA influx
↑contraction↑ventricular ejection↓EDV&ESV↑CO:↓Sympathetic, ↓HR, ↓TPR↑Renal perfusion, ↓Edema
SA:↓rateAtria:↓refractory periodAV:↓conduction velocity ↑ refractory periodPurkinje/Ventricle: ↓refractory period (slight)ECG: ↑PR,↓QT interval↑venous toneKidney: diuresis
Heart failureCHF + Atrial fibrillationSevere/Chronic CHF + LV systolic dysfunctionAtrial flutter/fibrillation: ↓Av node conduction↑AV node ERP
Initial:GIT: AnorexiaNausea, VomitingDiarrheaCNS:Elderly-disorientation & hallucinationsColor vision disturbanceAntidote: Lower dose
Cardiac:Delayed afterdepolarizationsVentricles:BigeminyFibrillation/tachycardiaHeart blockECG: PVB, inverted T wave, depressed ST segment; tachycardia, fibrillation, arrestSA: ↓rateAtria: ↓refractory periodarrhythmiasAV node: ↑refractory periodarrhythmiasPurkinje/Ventricles: Extrasystoles, tachycardia, fibrillations
↓K+:Mild: skip 1-2 doses; oral K+ supplementation <5 meq/LSevere/Suicidal: ↑K+ levels; not give K+ supplements
Suicide/severe poisoning: Digoxin antibodiesFab fragments bind & inactivate drug
Arrhythmias: Antiarrhythmic- lidocaine, phenytoin
+ 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
β 1 agonists Dobutamine Drug + β recepto
↑CO↓ventricular filling
Acute Heart Failure ArrythmiasTachycardia
Less arrythmogeni
r↑cAMPactivation of PK-Aphosphorylation of Ca channel↑Ca2+ flow into cellmyofibrils↑contraction force
pressure c & less tachycardia vs dopamine
Dopamine ↑BP Acute Heart Failure, raise BP
Phosphodiesterase Inhibitors
AmrinoneMilrinone
PDE are enzymes that inactivate cAMP & cGMPPDE inhibitors: X PDE↑cAMP & ↑cGMP
Inotropic agentVasodilation
Severe Heart Failure ↑MortalityNausea, VomitingArrhythmias↑Liver enzymeThrombocytopenia
Vasodilators ACE inhibitors EnalaprilLisinopril
Non selective vasodilator: Arteries & Veins
X ACE (kininase 2)↓angiotensin 2↓sympathetic activityVasodilation↓afterload↓aldosterone↓salt & water retention↓venous return↓preload
Non selective vasodilator: Arteries & Veins↓afterload & ↓preload
CHF:First line↓ventricular dilation↓long term remodeling↑efficacy of diuretic treatment↓mortality & morbidityAsymptomatic patients w/ LV dysfunction + no edemaSymptomatic patients: ↓preload and afterloadHypertensionMIDiabetic Nephropathy
First dose hypotension (post diuretics)Cough (↑bradykinin)HyperkalemiaDysguesia, rashes, urticarialAcute Renal Failure; angioedemaTERATOGENIC
Angiotensin Receptor Blocker
LosartanValsartanIrbesartanCandesartan
No cough Block AT-1 receptor (angiotensin-2 receptor)No effect on ACEBradykinin metabolized
ACEI intoleration due to coughCHF: all stagesHypertension
Hypotension↑K+AngioedemaTERATOGENIC: fetal damage
Nitrate Isosorbide Dinitrate
Venodilator Venodilator↓preload
Dyspnea NOT FIRST LINE DRUGSIsosorbide dinitrate + hydralazine↓remodelling(africans)
Hydralazine Arteriole dilator Dilates arteriole↑CO↑cGMP-smooth muscle
Arteriole dilator Patients w/ increased fatigueAntihypertensive-pregnancy + α methyl DOPA
Sodium Nitroprusside
Arteriole + Veno dilator
↑NO↑cGMP Arteriole + Veno dilator↓afterload & ↓preload
CHFHypertensive emergency
Diuretics Loop diuretics FurosemideBumetanideTorsemide
↓venous pressure↓preload↓systemic pulmonary edema
↓cardiac size↑pump efficiency↑CO
CHF:FIRST LINEFurosemide/loop diuretic: Acute pulmonary edema, severe chronic failureSpirinolactone: Severe
Hypokalemia: leads to digoxin interactionHypervolemiaOtotoxicityHyperuricemia: GoutMetabolic alkalosisHyperlipidemia
Thiazide diuretics
ChlorothiazideHydrochlorothiazide
Aldosterone Spirinolactone
antagonist Eplerenone chronic heart failure, ↓morbidity &↓mortality
β blockers BisprololCarvedilolMetoprolol
↓catecholamines:↓HR↓symptoms↓Myocyte apoptosis↓remodelling
Start w/ low doses↓mortality in stable severe heart failure↑EF,↓HR, ↓symptomsLong term:↓death rate, ↓symptoms, ↑sense of well being, better clinical status
Stable chronic heart failureMI historyAsymptomatic patients w/ ↓LVEF
Neseritidine BNP, IV continuous infusion Acute Heart FailureBosentan Endothelin receptor
antagonistSevere Pulmonary Hypertension
↑survival in CHF
ACEI, ARB, β blockers, spirinoloactone, hydralazine+nitrate
Stage A: High risk, No symptoms↓Risk factorsTreat: hypertension, hyperlipidemia, diabetes, obesity
(ACEI/ARB for vascular disease)
Stage C: Structural disease, Symptoms↓ Na, H20, WorkDiuretics, ACEI, ARBDigitalis: systolic dysfunction + 3 HS/atrial fibrillationβ blockers ( in stable class 2-4)Spirinolactone
Drugs causing CHF NSAIDCCBAnti arrhythmic (some)Alcohol
Chronic Heart Failure
↓work, ↓Na & H20ACEI or ARBThiazide diuretic β blocker (in stable class 2-4)Digitalis (if systolic dysfunction/atrial fibrillation)Nitrate/hydralazine (vasodilator)Cardiac resynchronization (if wide QRS)
Acute Heart FailureCan be due toAMIAnemia, fever↑metabolic demand↑exertion, ↑emotion, ↑Na
↓Power: inotropes, vasodilatorsPulmonary congestion: diuretics
Stage B: Structural disease, No symptoms↓Risk factorsTreat: hypertension, hyperlipidemia, diabetes, obesity
(ACEI/ARB, β blockers)
Stage D: Refractory Symptoms↓ Na, H20, WorkDiuretics, ACEI, ARBDigitalis: systolic dysfunction + 3 HS/atrial fibrillationβ blockers ( in stable class 2-4)SpirinolactoneCardiac resynchronizationCardiac transplant
SHOCKType of Shock Mechanism Treatment
Hypovolemic/Oligemic shockLow Volume
Internal & external fluid loss↓preloadHemorrhagic/Non HemorrhagicTraumaNon traumatic: Vaginal, GI, GUBurns, DiarrheaVomitingDiuresis, SweatingThird Space Loss:Pancreatic, peritonitis, bowel obstruction
Volume resuscitation: rapid infusion-isotonic saline, ringers lactateNaHCO3-correct acidosisInotropic support following volume support-Dobutamine, DopamineO2Acute hemorrhage/anemia: Whole Blood & plasmaAbsence of Blood & plasma: Colloidal plasma expandersHuman albumin, Dextran, HydroxyethylstarchCrystalloid plasma substitute: superior to colloids-Normal saline, 5% dextrose, ringer lactate
Neurogenic shockLow Resistance
Cervical spinal cord injury/severe head injuryloss of sympathetic vasomotor tonearteriolar & venodilationpooling of blood in post capillary capacitance blood vesselpooling of venous system↓venous return & ↓cardiac output
Penylephruine/Norepinephrine↑vascular resistance↑MAPIV fluids for relative hypovolemia
Cardiogenic shockPump Failure
Severe LV dysfunctionsystemic hypoperfusionMI, acute myocarditis
MI:Morphine,O2, nitroglycerine, aspirin, alteplase (fibrinolytic), metoprolol (β blocker), captopril (ACEI), heparin (anticoagulant)Dopamine:Low dose-dilates renal vascular bedModerate dose- +ve chronotropic & inotropic effectsDobutamine: +ve chronotropic & inotropic effectsIV fluids: maintains adequate blood volume
Septic/Bacteremic/Endotoxic shock
Severe infection & tissue hypoperfusionGN (E coli)>GP (staph)
Infection treatment, Hemodynamic & Respiratory support w/in 1hr of presentationAntimicrobial:Empirical: effective against both GN & GP microorganismAfter microbial culture: appropriate antimicrobial treatmentRemove focal source of infectionNaHCO3-corrects acidosisVasopressor-for hypotensionO2Recombinant activated protein C: Sepsis associated w/ excess inflammatory response & altered coagulation & fibrinolysisAnti-inflammatory & Anti-apoptoticSeptic shock w/ adrenal insufficiency: Glucocorticoids (hydrocortisone 100 mg IV TID)
Anaphylactic shock Histamine release & other mediators Adrenaline: 0.5 mg of 1:1000 IMreversal of hypotension, bronchospasm, laryngeal edemaIV fluidsHydrocortisone hemisuccinate: 100mg IV/IM- inhibit late phase of allergic reactionChlorpheneramine: 10-20 mg slow IVO2, assisted ventilation
DopamineD1, D2, α1, β1Low dose: 2 µg/Kg/minD1dilates renal vascular bedModerate dose: 2-10 µg/Kg/minD1,β1+ve chronotropic & inotropic effectHypovolemic, Cardiogenic, Septic
Dobutamineβ1 selectiveinotropic w/ afterload reduction(peripheral vasodilator)minimize cardiac O2 consumptionCardiogenic shock-pump failure due to MI
Norepinephrineα1, α2, β1Strong vasoconstriction↑BPShock w/ severe hypotension
Phenylephrineα1 agonistStrong vasoconstrictorNeurogenic shockVasopressin:Catecholamine resistant shockMilrinone:PDE inhibitorPotent inotrope & chronotrope
Shock treatment:Early recognitionABC resuscitationFluid restorationVasopressors (AFTER fluid restoration)Restore O2 deliveryControl inciting pathological processMaintain vital organ function
Hypovolemicshock
Endotoxic shock
Cardiogenic shock
Anaphylactic shock
Volume replacement
YES YES NO POSSIBLY
Dopamine YES YES YES POSSIBLY
Dobutamine POSSIBLY YES YES NO
Adrenaline NO NO NO YES
Glucocorticoids NO YES NO YES
Antihistaminics NO NO NO YES
HEMATINICSOral Fe Ferrous Sulphate (32%)
Ferrous Fumarate (33%)Ferrous Gluconate (12%)Colloidal Ferric Hydroxide (50%)
PreferredFerrous>Ferric absorptionEmpty stomachUpper intestineabsorbed
ADRsEpigastric painNausea, vomiting, heartburnMetallic tasteStaining of TeethBloating
Parenteral Fe
Iron DextranIV/IM
Iron Sorbitiol-CitrateIM
IM-deep gluteal injectionZ technique-avoid skin staining2ml-daily/alternate days5 ml each side on same dayIV-0.5 ml Fe Dextran after test dose over 5-10 minInfusion-diluted in 500 ml glucose/salineFe sorbitol-not iv
ADRsLocal:PainSkin PigmentationSterile abscessSystemic:Fever, headache, joint pain, flushingPalpitation, chest pain, dyspneaLN enlargementAnaphylaxisRenal Disease-X Fe sorbitol
USESFe deficiency anemia(treatment & prophylaxis)Megaloblastic anemiaFeCl3-astringent in throat pain
↑MWIM(locally bound)/IVNot excretedAbsorbed through LymphaticsNot transferrin boundTaken up by macrophagesslowly available to erythron
↓MWIM-Not locally bound30 % excretedAbsorbed through CirculationTransferrin bound
Directly available
Fe overload
Normal-2.5-3mg>7 mgtissue damageAcute Fe Poisoning:>60mg/KgVomiting, Abdominal Pain, HematemesisDiarrhea, LethargyCyanosis, Dehydration, AcidosisConvulsionsShock, CVS collapse
Management:Prevent further Absorption:Induce vomiting/gastric lavageOral egg yolk & milkcomplex ironActivated charcoal uselessBind & remove absorbed Fe:Chelating Agent: DesferroxamineDTPA/Ca edetateBAL contraindicatedSupportive Measures:Correct fluid/electrolyte balanceCVS supportConvulsions: Diazepam
Hemopoetic GFErythropoetin: peritubular cells of kidney↑RBCMCSF, GCSF↑WBCThrombopoetin↑plateletsStem cell factorIL
Megaloblastic state
B12/Cobalamin deficiency:Gastric failure:Pernicious anemiaTotal gasterectomyIleal failure:Crohn’s disease: regional enteritisIleal resectionTropical sprueCompeting organism:Bacterial overgrowth (blind loop)
Folate deficiency:Folate poor diet: Alcoholism, poverty↑ Folate requirement:PregnancySevere hemolytic anemiaSevere psoriasisDrug therapyTropical sprue
Clinical features:B12 & Folate:Megaloblastic anemiaFatigue, weight loss, fundal hemorrhage, diarrhea, fever, sore tongue, appetite loss, jaundiceB12 deficiency:Paraesthesia, neuropathy, dementia, demyelination of spinal cordPernicious anemia: Family & personal history of vitiligo, Autoimmune thyroid disease
Treatment:Transfuse (care)B12-oral or parenteralFolate tabletsSevere cases: hypokalemia
Epoetin:r Human Erthropoetin Uses:Chronic Renal FailureCancer ChemotherapyAIDS anemiaPremature infantsDose: 25-100 IU/Kg/SC IV 3x a WkAdverseFlu like symptomsMild HypertensionEncephalopathyThrombosis
Diphyllobothrium latum ↑Fe & Folate demand
DRUGS AFFECTING BLOOD ELEMENTSDisease/Condition Causative Drugs/Causes Treatment/Therapeutic Drugs Adverse effectsG6PD-Hemolytic anemia
Antimalarials:PrimaquineChloroquineFansidarMaloprim
Stop drugTreat underlying infectionsSevere anemiablood transfusionHemoglobinuriamaintain good renal flowavert renal damageNeonatal jaundicephototherapy
Sulfonamides:SulfacetamideCo-trimexazoleDapsoneAntibiotics:ChloramphenicolFurazolidoneNiridazoleNalidixic acidNitrofurantoinAntidiabetics:GlibenclamideAnalgesics;High dose ASPIRINVitamin K analoguesNaphthalene
Immune Hemolytic Anemia
Penicillin-High Dose:Ab against drug-RBC complex
Stop DrugCORTICOSTEROIDS:PrednisoneFIRST LINEAzathioprine, Cyclosporin, Cyclophosphamideused when other measures failSplenectomySevere Cases:Blood TransfusionsFolate
QuinidineRifampin:Drug-ag-ab deposits complement on RBC surfaceMethyldopaFludarabine
Chemical AgentsHemolysis
Dapsone-High Dose Stop DrugSevere Anemia: Blood Transfusion
Wilson’s Disease-Cu-High Dose
Poisoning: Pb, Chlorate, Arsine
Thalassemia Regular Blood TransfusionFolate-regular useSplenectomy: 6yrs+Hepatitis B vaccineAllogenic BM transplant
Iron OverLoad:Liver damageEndocrine: growth failure, delayed/absent puberty, DM, hypothyroidism, hypoparathyroidismMyocardium Siderosis
Iron Chelator:Parenteral: Desferoxamine1-2g IV or 20-40 mg/Kg SC w/ each unit of bloodAdverse :Rapid IV: hypotensionIdiosyncratic reactions: Flush, RashPulmonary, Neurosensory toxicityOral: Defipirone, Deferasirox
Endocrine therapy: GH, insulin, Ca, Vitamin D
Aplastic Anemia Chemicals:Benzene, DDT, insecticides, Hair Dye
General Treatment:Stop Drug/ChemicalAnemia: Blood transfusions, Platelet concentratesInfections: Prevent & Treat-cultures, Broad spectrum prophylactic antibiotics, antifungals, GCSFSevere ThrombocytopeniaFibrinolytic Inhibitors:Tranexamic Acid or Aminocaproic AcidPlatelet transfusionAllogenic Stem Cell Transplantation
Drugs:Anticancer:BusulphanCyclophosphamideAnthracyclinesNitrosoureas
Idiosyncratic:ChloramphenicolSulphonamideGold
Specific Treatment:Anti Lymphocyte Globulin (ALG) & Anti Thymocyte Globulin (ATG): ↓cytotoxic T cellsAdverse:Fever & Chills: PrednisoloneSerum 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 TransplantationNeutropenia Anticancer Drugs:
Alkylating agents-non selective neutropeniaGeneral Treatment:Stop DrugPrevent & Treat infections:Bacterial UsuallyCan also be:Viral, Fungal, Protozoal
Antibiotics:ChloramphenicolsSulfonamidesCo-trimexazoleCephalosporinsAntipsychotics:ChlozapineChlorpromazine
Specific Treatment:GCSFGM-CSFAutoimmune Neutropenia: Corticosteroids & SplenectomyRituximab: Anti CD-20 (Monoclonal Antibody)
Antithyroids:CarbimazoleAnti-Inflammatory:Phenylbutazone
Gold SaltsAnti-Epileptic:PhenytoinCarbamazepinePenicillamineTiclopidine
Thrombocytopenia Bone Marrow Suppression: Anticancer, EthanolChloramphenicol, Co-trimoxozole, Arsenic
General Treatment:Blood Transfusion/Platelet Concentrates
Immune:Analgesics, Anti-inflammatory: Gold SaltsAntibiotics: penicillin, trimethopterin, sulfonamidesAntiepileptic: Diazepam, CarbamazepineDiuretics: Acetazolamide, FurosemideAntidiabetics: ChlorpropamideDigoxin, Heparin, Methyldopa, Quinidine
Specific Treatment:Corticosteroids: Prednisolone (High Dose)Splenectomy: Patients w/ steroid failure or in need of high dose steroidsImmunoglobulin: Rituximab (anti CD 20); high dose modify autoAb productionImmunosuppression: Azathioprine, Cyclosporin, Cyclophosphamide when other measures failMegakaryocyte Growth Factor: OPRELVEKIN (IL 11)
Platelet Aggregation: Heparin
Erythropoetin:Hb, Erythropoesis, circulatory reticulocytesEPOETIN α, DARBOPOETIN α: IV, SCUses:Anemia due to CRF/AIDS, cancer/drugsAnemia in premature babiesPre-Operationto blood transfusionsAdverse: Thrombosis, BP
Myeloid Growth Factor:rG-CSF: Filgrastim neutrophilsrGM-CSF: Sargramostim neutorphils, eosinophils, monocytesUses:Post chemotherapy, radiotherapy, autologous SC transplantPeripheral mobilization of SC for autologous SC transplant (G-CSF)Severe neutropenia, Aplastic anemia
Megakaryocyte Growth Factor:Oprelvekin: IL-11ThrombopoetinUses:Thrombocytopenia /after cancer therapyAdverse Effects:Fatigue, Headache, Dizziness, Fluid RetentionCVS effects: Dilutional anemia, dyspnea, Transient Atrial Arrythmia
ANTI-PARASITICDisease Class Drug Mechanism Uses Adverse EffectsAntimalarial Erythrocitic Schizonticide Chloroquine Degradation of
RBC HBFast & Long Acting
Prophylaxis & Cure of ALL types of MalariaInfectious MononucleosisRheumatoid Arthritis
toxicity; side effectsGIT-A/N/V, epigastric painCVS: IV; BP; arrhythmiaCNS: toxicityEye: retinal damageEar: Hearing Defects
Mefloquine Intermediate & Long Acting
Multidrug Resistant Plasmodium falciparum malaria
Not ParenteralAvoid in cerebral/complicate malariaResistance
Quinine Multidrug Resistant malariaCerebral malaria+ Tetracycline=effectNocturnal muscle cramps, varicose veins, myasthenia gravis
effective, toxicity than chloroquineHighly toxic8-10 g-fatalCinchonism: CTZ damage, vomiting, tinnitusHemolysisPregnancyAbortion
Sulfonamide (sulfamethopyrazine/sulfadoxine)+Pyremethamine (S/P)
Slow and Long actingErythrocytic phase of P. falciparumAntifolate (like Cotrimoxazole)
P. falciparumcurativeToxoplasmosisfirst choice
SulfonamideSerious toxicityExfoliative dermatitis, Steven Johnson syndromeNot prophylacticSingle Dose
Tetracyclines Weak & Slow acting
All Plasmodium species+Quinine or S/PChloroquine resistant FalciparumDoxycycline (100 mg/day): Second Line Prophylactic-Chloroquine resistant Falciparum malaria
X Pregnant, LactatingX Children <7 yearsNEVER USED ALONE
Blood Schizonticide Halofantrine Mefloquine like activity
Multidrug Resistant P. falciparumP. vivaxUsed when other drugs not working
GITVentricular Arrhythmia
Artemesinin DerivativesArtisunate: Water SolubleOral, IV, IMArtemether: Lipid SolubleArteether: IM
Fastest and Short actingProdrugsDamage ER & Protein synthesis in parasitesKills falciparum gametes
Multidrug Resistant Falciparum malaria treatment
+ enzyme inhibitors/anti-arrhythmic/anti-psychotic/anti-depressants arrhythmiasNot useful in prophylaxis
Tissue/Liver Phase acting/Exoxryhtrocytic
Primaquine Effective against Gametocytes & Hypnozoites
Prevent & Cure malaria relapse
GITG6PD: hemolysis
Filariasis Diethyl Carbamazine Selectively sensitize microfilariae for phagocytosis
FilariasisTropic Pulmonary Eosinophilia
GITFever, RashLN enlargement
Leishmaniasis Sodium Stibogluconate Inhibits –SH dependant enzymes of parasite
Kala Azar (L. donovanii) N/V, abdominal painPancreatitisKidney & Liver Damage
Trypanosomiasis Pentamidine Inhibits topoisomerase 2 & aerobic glycolysis
TrypanosomiasisLeishmaniasisAIDS patients: Pneumocystis jiroveci pneumonia
Highly ToxicStrong alkaline naturereleases HistamineanaphylaxisHeart, Liver, Kidney damage
Trypanosoma cruzi Nifurtimox/Benznidazole-Acute disease Chaga’s diseaseTrypanosom gambiense/rhodensiense
Early disease: IV suraminLate disease + CNS involvement: suramin + melarsoprol (crosses BBB) + corticosteroids (prevents reactive encephalopathy)
Sleeping sickness
Toxoplasmosis Sulfadiazine + Pyrimethamine+Falinic acid (prevents BM suppression)
Congenital/disseminated disease
Causal Prophylaxis:Pre/exo-erythrocytic phasecause of malariaPrevent clinical attacksProguanil: P. falciparumPrimaquine: all malarial species
Suppressive Prophylaxis:Erythrocytic Phase suppressionprevents malarial feverClinical symptoms suppressed; exoerythrocytic phase not affectedChloroquine: 300mgx2tabs/wk; 1wk before & 1 month after endemic area returnResistant cases: Proguanil 200 mg daily + Chloroquine 300 mg weeklyMefloquine 250 mg weekly-4wks after endemic area returnDoxycycline 100 mg 1day before to 4 weeks after endemic area return
Clinical cure: terminate episode of malarial feverErythrocytic SchizonticidesFast acting High efficacy: used aloneChloroquine, Mefloquine, Quinine, Amodiaquine, Halofantrine, Lumefantrine, Artemesinine, Atovaquone.Slow acting Low efficacy: used in combinationProguanil, Sulfonamides, Pyrimethamine, Tetracycline
GametocidalElimination of male & female gametes from patients’ bloodNot beneficial to patient; Reduces transmission to mosquitoPrimaquines & Artemesinines: Gametocidal to all speciesChloroquine & Quinine: Vivax gametes
Antimalarial Classification:
4-aminoquinolines: ChloroquineQuinoline – Methanol: MefloquineCinchona Alkaloid: QuinineBiguanides: ProguanilDiaminopyridine: Pyrimethamine8-aminoquinolines: PrimaquineSulfonamides: Sulfadoxine, SulfamethopyrazineTetracyclineSasquiterpine Lactone:Artesunate, Atemether, ArteetherAmino Alcohol: HalofantrineMannich Base: PyronaridineNaphthoquinone: Atovaquone
Most Antimalarials: Hemolysis in G6PD deficiency
Radical Cure: total eradication of parasite from bodyExo-Erythrocytic drugs + Erythrocytic drugs = total cureP. falciparum & P. malariae: clinical cure=erythrocytic schizonticides=erythrocytic parasite elimination is enough. No exoerythrocytic phaseP. vivax & P. ovale: Relapsing malariaerythrocytic & exoerythrocytic/hypnotic parasite elimination Exo-Erythrocytic drugs + Erythrocytic drugs
Falciparum Malaria:Chloroquine sensitive: Chloroquine + Primaquine (gametocidal)Chloroquine resistant:
Multi Drug Resistant Falciparum Malaria:Uncomplicated Acute Multidrug Resistant Falciparum Malaria:
Vivax Malaria:Chloroquine sensitive:Chloroquine + PrimaquineChloroquine Resistant:Quinine + Doxycycline + Primaquine
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
-Artesunate +Sulfadoxine+pyrimethamine (S/P)+Primaquine-Artesunate + Mefloquine-Artemeether + Lumefantrine-Quinine + DoxycyclineCerebral malaria: Chloroquine sensitive malaria drugs IV
ACT-Artemesinine based Combination TherapyArtemesinine + Erythrocytic Schizonticide
DoxycyclineAreas w/ multidrug resistant P. falciparum
PrimaquineTerminal Prophylaxis of P. vivax & P. Ovale
ANTIRETROVIRALSClass Drugs Mechanism Uses Adverse Effects ResistanceNucleoside & Nucleotide Reverse Transcriptase Inhibitor
Zidovudine (AZT) Deoxythymidine AnalogAZTThymidine KinaseTriphosphate formCompetitive Inhibition of dTTP for Reverse Transcriptase EnzymeCauses Chain Termination
IV & OralHIV 1, HIV 2, HTLVHIV treatment: progression & survivalPrevents Mother to Child HIV transmission
Myelosuppression: Neutropenia, AnemiaGI intolerance: N/VHeadaches, InsomniaCrosses BBBMetabolite in urine
Mutations in reverse transcriptase geneProlong therapy & Monotherapy
Stavudine Thymidine Analog Peripheral NeuropathyLipidystrophy
Didanosine Synthetic Deoxyadenosine Analog
PancreatitisPeripheral NeuropathyD/N/VAbdominal Pain
Zalcitabine Cytosine Analog Peripheral NeuropathyN/VHeadache
Lamivudine Cytosine AnalogAbcavir Guanosine Analog
More effectiveFatal Hypersensitivity
Non-Nucleoside Reverse Transcriptase Inhibitors
Nevirapine Binds to Viral Reverse TranscriptaseRNA & DNA dependent DNA polymerase blockadeSubstrate & Inhibitors of CYP3A4Do not compete w/ nucleoside triphosphatesDo not require Phosphorylation
Prevents HIV transmission from mother to neonate at labor/delivery
DelavirdineEfavirenz TERATOGENIC
Protease Inhibitors Indinavir Protease: Cleaves large precursor polyprotein moleculefunctional componenetsInhibit Protease (late step in replication) prevent spread of infection
Nephrolithiasis Lipidystrophy: Abdominal Obesity, Buffalo Hump, Limb & Face wastingDyslipidemiaGI intoleranceDizzinessNumbnessRashesHeadacheLimb & Facial tinglingAstheniaHyperlipidemiaInsulin resistance
Ritonavir FatigueInhibits CYP3A4
Squavinavir PhotosensitivityNelfinavirAmprenavir
Fusion/Entry Inhibitor
Enfuvirtide (T-20) Binds to gp-41 subunit of viral glycoprotein envelopeprevents conformational changes required for fusion of viral &
cellular membranesBlocks FusionPrevents entry into/infection of CD 4 cells
Integrase Inhibitor RaltegravirAnti HIV regimens:Zidovidine + Lamuvudine + Lopnavir (PI)Zidovidine + Lamuvudine + Efavirenz (NNRTI)
Post Exposure Prophylaxis:Low Risk: Zidovidine (300 mg) + Lamuvidine (150 mg)2xdaily for 4 weeksHigh Risk:+ Indinavir (800 mg)3xdaily for 4 weeks
HAART:2 NRTI + 1 PI (+/- ritonavir)
2 NRTI + 1 NNRTI
THROBOLYTICS, ANTITHROMBOTICS AND COAGULANTSClass Drug Description Action Uses ADR ContraindicationsThrombolytics / Fibrinolytics Streptokinase Non enzymatic
proteinβ hemolytic streptococciProactivator plasminogen complexcatalyzes formation of plasmin
AMI: Thrombolytic Therapy-w/in 6 hrs of symptomsPeripheral Arterial ThrombosisCatheter & Shunt patencyPE + Hemodynamic InstabilitySevere DVTAcute Ischaemic Stroke: rTPA w/in 3 hrs of symptomsPeripheral Vascular Disease
Action blocked by Antistreptococcal Ab
1Year should be elapsed before next use
Allergy, Hypotension-generating Kinins
Serious Bleedingtreated w/ tranexamic acid, fresh plasma or coagulation factors
Absolute Contraindications:Neurosurgery/Head trauma <2 mtsSevere Active Bleeding/ Internal HemorrhageCerebrovascular Hemorrhage <6 mtsCerebral tumor/aneurysm
Relative Contraindications:Recent Major TraumaInvasive Surgery < 10 daysGI/genitourinary bleedingRecent CardioPulmonary ResuscitationPeptic Ulcer <3 mtsPregnancyUncontrolled HypertensionThrombocytopenia
Urokinase Enzyme-Human urineCultured Human Renal CellsNon-AntigenicPotent Direct Plasminogen Activator
Non Antigenic
Recombinant Tissue Plasminogen Activator:AlteplaseDuteplaseReteplase
rDNA technologyExpensive
Better than streptokinase & urokinase in dissolving older clotsDoes not act on circulating plasminogenNon Antigenic
Anistreplase Anisoyloted Plasminogen Streptokinase Activator Complex (APSAC)Complex: Purified Human Plasminogen + Bacterial Streptokinase
Rapid action Clot selectivity Activity on plasminogen associated clots than free blood plasminogenThrombolytic Activity
Allergies BleedingHypotension-Kinins
Anti-Coagulant(AntiThrombotic)
Parenteral Anticoagulant
Indirect Thrombin Inhibitor
Unfractionated Heparin(UFH)
MW: 5000-30,000
Sulfated Mucopolysaccharide
IV/SCNot given IMhematoma formationImmediate onset
HeparinActivates Anti Thrombin 3 (AT-3)Inhibits Factors 2a (Thrombin), 9a, 10aBleeding timeClotting timeaPTT
DVT & PE:Prophylaxis-for bed rest, high risk surgeries, Cancer- Low dose UFH, LMWH, FondaparinauxTreatment-UFH,
Bleeding: risk: careful patient selection, Dosage control, monitor aPTT
Heparin Induced Thrombocytopenia (HIT):Ab formed to Heparin & Platelet Specific Protien - Platelet Factor 4
Drug hypersensitivity, HITActive Bleeding/Risk,Intracranial Haemorrhage, Active TB, Hemophillia, TTP, Recent Surgery-CNS, eye, postateThreatened AbortionBrain & Spinal Cord InjuryAnaesthesia: Regional & Lumbar
4-6hrsMonitor:aPTT = 2-2.5 control
Does not cross Placenta
Inhibits Coagulation InVivo & InVitroInhibits Aldosterone SecretionLipemia clearingAnti-Inflammatory
LMWH for 5-6 days, then Warfarin for 3-6 mtsPregnant Women- 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
(PF4)Systemic hypercoagulable stateLeads to Venous ThrombosisPerform platelet count frequentlyTreatment: Direct Thrombin Inhibitor, Fondaparinaux
Allergy: Animal Origin-asthma, urticariaTherapy-Transient Alopecia Osteoporosis: >6 mts use
blockSevere Hepatic & Renal Impairment
Low Molecular Weight Heparins (LPWH):EnoxaparinDalteparinTinzaparin
MW: 3000-7000
Heparin Fragments Inhibits Factor 10aLess effect on Thrombin (2a)
Equally efficacious as UFHNo effect on CT, aPTTNo lab test requiredSCBioavailabilityLong T1/2Less frequent dosing1/2 weeklyBleeding, HIT
Prevention of DVT, PECannula patency in Dialysis patients
Fondaparinaux Anti Thrombin 3 mediated selective inhibition of Factor 10aNo effect on Thrombin (2a)SCLong T1/2: 15 hrs
PE, DVTHITAMI
Direct Thrombin Inhibitor
Hirudin/Lepirudin (Bivalent DTI)Specific irreversible Thrombin Inhibitor
Hirudin: Leech SalivaLepirudin: recombinant form
Directly bind to active site of Thrombin
HITAnaphylaxis
Bivalirudin (Bivalent DTI)
Coronary Angioplasty
Argatroban (Univalent DTI)
HITCoronary Angioplasty in HIT patients
Oral Anticoagulant
Vitamin K Antagonist
Warfarin Inhibits Vit K EpoxideVit K Hydroquinone (active form)
Inhibits Vit K EpoxideVit K Hydroquinone (active form)
Bleeding: Common-Haematuria, Epistaxis, Bleeding Gums, Uterine, Intracranial Ulcer-FATALTreatment: Vitamin K (antagonist),
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 KInhibiting Factors (coagulation)-Thrombosis-Pregnancy: synthesis of Clotting factors-Hypothyroidism: metabolism (destruction) of clotting factors-Genetic warfarin resistance
Inhibits synthesis of Vit K dependent Factors 2,7,9,10 (TENS)
Slow Complete AbsorptionDelayed onset: (1-3 days)plasma protein bindingCrosses Placenta & Secreted in MilkMetabolized in Liver
Dose Regulation:Monitor PT-reduce to 25% of controlINRFull effect: 4-5 days even if INR reaches therapeutic level in 1-2 days
PK: Enzyme Induction & Inhibition, PP bindingPD: Synergism-impaired hemostasis/clotting factor synthesis (hepatic disease), Competitive antagonism-Vit K, Hereditary resistance to oral anti coagulants
Fresh Blood/Plasma Infusion
Teratogenic: Fetal Warfarin Syndrome- Fetal Hemorrhage, Abnormal Bone Formation
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 HypersenstivityDirect Thrombin Inhibitor
Dabigtaran No routine INR monitoring requiredFewer Drug Interactions compared to Warfarin
Prevent Stroke & Thromboembolism in Atrial Fibrillation
In Vitro Calcium Chelators
Ethylene Diamine Tetra Acetic Acid(EDTA)Citrate
Prevent Blood Clotting in Test Tubes
Lithium HeparinAntiPlatelet Prostaglandin Synthesis Aspirin Inhibits COX & MI Prophylaxis Arterial
Inhibitors Thromboxane Synthase IrreversiblyTXA2 synthesis in Platelets Bleeding Time in vivoLow Dose: 75-100 mgPlatelets exposed to aspirincannot synthesize new enzyme
Unstable AnginaCerebrovascular Disease
Thrombus-White Thrombus
Prevent Reinfarction in Active MI & IHD
Primary & Tertiary prevention of MI post MI
Prevent stroke in cerebrovascular disease & transient ischemic attacks
Patency of implanted bypass in CABG:Aspirin + Abciximab
ADP Receptor Blocker ClopidogrelTiclopidine
Inhibits Platelet Aggregation
(ADPCa2+ (2nd messenger)Gp 2b/3a active)
Blocks ADP Receptor (P2Y12)ADPplatelet aggregationADP-RBinhibits aggregation
Aspirin Intolerant PatientTransient Ischemic AttacksStroke, Unstable AnginaCoronary Stent
Nausea, Diarrhea, LeukopeniaThrombocytopenic PurpuraClopidogrel: Less ADR, Safer
Glycoprotien 2b/3a Receptor Inhibitor
Abciximab Chimeric Monoclonal Antibody
Chimeric Monoclonal Antibody against Gp 2b/3a receptor
PCIAMI/Acute Coronary Syndromes
EptifibatideTirofiban
Parenteral Occupies ReceptorInhibits Ligand Binding
PDE Enzyme inhibitor Dipyridamole Weak effect on Platelet Aggregation
Inhibits Platelet PDE enzyme cAMPPGI2Weak effect on Platelet Aggregation
+Aspirincerebrovascular ischemia+WarfarinArtificial Heart Valves
Prasugrel Platelet Inhibition Platelet InhibitionBetter Than ClopidogrelPlatelet Inhibition
ischemic eventsThrombolysis in AMI
Ticagrelor Oral, reversible Direct Inhibitor of ADP Receptor (P2Y12)Reversible
Fibinolytic Inhibitors / Antifibrinolytics
Amino Caproic Acid Treat Overdosage of FibrinolyticsHemophilics: Limit excessive bleeding after SurgeryPrevent recurrence of SubArachinoid HemorrhageAbruptio Placenta, Post-Partum hemorrhage, Menorrhagia
Tranexaemic Acid Oral7 x more potent than ACA
Aprotinin CABG Surgery: Blood LossProtamine Sulphate Heparin Antagonist Heparin Antagonist
Basic ProtienFish SpermSlow IV1 mg Protamine Sulphate for every 100 units of Heparin remaining in patient
Combines w/ Heparin as an ion pairStable complex devoid of anticoagulant activity
BP, HRDyspnea, Flushing
Coagulants Vitamin K K1-Phytonadione-Fat soluble-PlantsK2-Menaquinone-BacteriaK3-Menadione-Fat/Water soluble-Synthetic
Deficiency due to:Liver Disease, Malabsorption Syndromes, long term antibiotic use
Deficiency Symptoms:Bleeding: Urine, Nose, GIT, Skin-Ecchymoses
Synthesis of Clotting Factors:2, 7, 9, 10 (TENS)In Liver
Deficiency of Clotting FactorsNewbornWarfarin Overdose: Phytonadione
Toxicity: BP, FlushingMenodione: Kernicterus in Newborns-Treat by Phytonadione
Plasma Fractions Factor 8Anti-Hemophilic Factor
Treat Hemophilia A
Prothrombin Complex ConcentratesFactor 9 Complex
Treat Hemophilia B (Factor 7 deficiency)
Factor 7a Liver Disease, Blood LossFactor 7 deficiency
CryoprecipitateFibrinogen
Hemophilia ALiver DiseaseDIC
Megaloblastic Anemia:
Hb:RBC:WBC: =/Platelet: =/Reticulocyte: Hct: MCV: MCH: =/MCHC: =Serum LDH: Serum Bilirubin: B12 &/or Folate: B12<100pg/mlPBS: hypersegmented neutrophils, macroovalocytesBM: erythroid hyperplasiaPenicious Anemia:Serum Ab to parietal cellsSerum Ab to IFAchlorydia (HCl –ve)
Aplastic anemia:Congenital: FanconiSecondary: Radiation, Chemical, Drugs: Chloramphenicol, Infections: Parvovirus B19, HIV, Hep A, B, C
DD:Severe Megaloblastic anemia w/ pancytopeniaMDSPrimary MyelofibrosisMarrow Fibrosis secondary to any other disease
Hb:RBC: WBC:Platelet:PBSBM: Trephine-dry tap w/ hypocellular imprints
Fanconi:Kidney & Spleen hypoplasiaHypoplasia of bone: Thumbs/radiiShort stature
PRCA:Congenital: Diamond BlackfanAcquired-Primary-AI destruction of erythroid precursorsSecondary:-Thymic tumor-thymoma-Malignancy-CLL, lymphoma-drugs, pregnancy-AI-SLE-Virus: Parvovirus B19, EB
Myelophthisic anemia;Space occupying lesions:Marrow infiltration: metastatic tumor, granulomaMarrow Fibrosis: Primary, Secondary to hemmatopoetic malignancies
Anemia of Chronic Disease:Normocytic Normochromic/Mildly microcytic, hypochromicMCV: 77-82;rarely<75Hb rarely<9ReticulocytopeniaSerum FeTIBCSerum Ferritin: =/BM Fe store: Perl’s stain: =Hepcidin: caused by IL1 & TNF
Iron Deficiency Anemia:Microcytic HypochromicMCV: MCH: Hb: RBC: Serum Fe: TIBC:
Hereditary Spherocytosis:ADHb: Reticulocytosis: 5-20%PBS: spherocytesDAT: normalOsmotic Fragility:
PlasmodiumFalciparumMalariaeVivaxOvale
Malaria Female Anopheles Mosquito
Infective: SporozoitesDiagnostic: Trophozoites, Schizonts, gametocytes
Sexual:Gametogony: MosquitoSporogony: humansAsexual: Schizogony: humans
Sporozoites liver schizonts (hypnozoites) blood RBC trophozoites Schizonts (merozoites) or gametocytes mosquito gut ookinete oocysts sporozoites
Anemia, cyclic fevermerozoites lyse RBC & get released
Cerebral Malaria: falciparum-aggregates of RBCs occlude capillaries
Relapse: hypnozoites- Vivax Ovale
Toxoplasma gondii Congenital ToxoplasmosisToxoplasmosis
Cat-definitive hostHumans: intermediate host
Infective: Ocysts from cat feces/raw meattransplacental
Oocystcat ingests tachyzoitestissue bradyzoites/oocysts
Trophozoites: Brain, eye, LiverTissue Cysts-enlarge & cause symptomsEncephalitis in AIDS patients: impaired CMI
Trypanosoma cruzii Chaga’s Disease Reduviid Bug Infective: TrypomastigotesDiagnostic: Trypomastigotes/ Amastigotes
Blood meal Trypomastigotes Reduviid Bug Midgut: Epimastigotes Hind gut: Trypomastigotes defecated –human amastigotes trypomastigotes
Myocarditis: amastigotes kill myocytesNeuronal Damage: Megacolon, Megaoesophagus
Trypanosoma Brucie:Gambiense & Rhodensie
African Tryposomniasis: Sleeping Sickness
Tsetse Fly-both sexes
Gambiense: west Africa-HumanRhodensie: east Africa-Animal-antelope
Infective: metacyclic trypiomastigotesDiagnostic: trypomastigotes
Blood mealTrypomastigotes Midgut: epimastigotes (procyclic) salivary glands: trypomastigotes (metacyclic) Blood stream
Trypomastigottes infect braindemyelinatin Encephalitis
Cervical LN’opathy winterbottom’s sign
Leishmania donovanii
Kala- AzarVisceral Leishmaniasis
Sandfly- Phlebotomus, Lutzomyia
Animal: Dog, small carnivores, rodents
Human: India
Infective: PromastigotesDiagnostic: Amastigotes
Blood MealAmastigotes Midgut: promastigotes Migrate to pharynx/proboscis human: macrophages Amastigotes
Kill RE cellsLiver, Spleen, BM
Leishmania Tropicana & Mexicana
Cutaneous Leishmaniasis
Reservoir: Forest rodents
Leishmania Brazilensis
Mucocutaneous Leishmaniasis
Wuchereria bancrofti
Filariasis Female Anopheles & Culex Mosquito
Definitiev host: Humans
Infective: Larvae (L3)Diagnostic: Microfilariae
Mosquito bites wound infective larvaelymphatics: Adultsblood: microfilariae
Adult worms block Lymphatics