==ANS==

**Holinergicki lekovi**

Lekovi sa indirektnim dejstvom

Lekovi sa direktnim dejstvom

- Estri holina (acetil holin, metaholin, karbahol, betanehol)

- Pilokarpin - Muskarin

Ireverzibilne antiholinesteraze

Reverzibilne antiholinesteraze

- Edrofonijum- Neostigmin- Fizostigmin

- Organofosfatni insekticidi (paraokson, paration, malation, OMPA)

- Bojni otrovi ( soman, sarin, tabun, VX)

www.belimantil.info

**Antiholinergicki lekovi**

Prirodni alkaloidi

Sintetske i polusintetske zamene

- Atropin - Skopolamin

Midrijatici

Spazmolitici

Antiparkinsonici

- Homatropin - Eukatropin - Tropikamid - Ciklopentolat

- Skopolamin-butil bromid (buskopan) - Metil-atropin

- Homatropin-metil nitrat - Drotaverin (no-spa)

- Triheksifenidil - Etilbenzatropin - Biperidin

www.belimantil.info

**Adrenergicki lekovi**Kateholamini

Adrenergicki vazokonstriktori

Adrenergicki bronhodilatatori

Adrenergicki stimulatori CNSa

- Adrenalin - Noradrenalin - Dopamin

- Nafazolin - Ksilometazolin - Oksimetazolin

- Efedrin - Fenilefrin - Metoksamin - Metraminol

Rezorcinoli

Sintetski kateholamini

Saligenini

- Izoprenalin

- Orciprenalin - Terbutalin - Fenoterol

- Salbutamol - Salmeterol

- Amfetamin - Metamfetamin

www.belimantil.info

**Antiadrenergicki lekovi**

Alfa adrenergicki blokatori

Beta adrenergicki blokatori

Neselektivni

Selektivni (alfa1)

- Fenoksibenzamin - Fentolamin - Tolazolin

- Alkaloidi razane glavnice(ergotamin, ergometrin, ergotoxin)

(Metrilergometrin, metisergid, bromokriptin)

(dihidroergotamin, dihidroergotoxin)

- Prazosin - Terazosin - Doksazosin

Neselektivni

Selektivni

- Propranolol - Oksprenolol- Alprenolol

- Timolol - Karvedilol- Sotalol

- Atenolol - Esmolol- Metoprolol

www.belimantil.info

**Antihistaminici**

H1 - antihistaminici

H2 - antihistaminici

- Difenhidramin - Dimenhidrinat - Prometazin

- Loratidin

- Hlorpiramin - Hlorfenamin - Feniramin

- Oksatomid - Astemizol - Terfenadin

- Cimetidin - Ranitidin

- Famotidin - Nizatidin

www.belimantil.info

==CNS==**Anksiolitici**

Benzodiazepini

Ostali anksiolitici

- Diazepam - Bromazepam - Lorazepam - Midazolam

- Buspiron - Zolpidem - Mepbromat

**Antidepresivi**Triciklicni Antidepresivi

- Amitriptilin - Protriptilin - Imipramin - Hlorimipramin - Doksepin

Inhibitori MAO- Nialamid - Tranilcipromid - Pargilin

www.belimantil.info

Selektivni inhibitori preuzimanja serotonina

Ostali

- Fluoksetin - Fluvoksamin - Paroksetin - Sertralin

- Moklobemid - Mianserin - Maprotilin - Trazodon

**Neuroleptici (antipsihotici)**Fenotiazini

Grupa 1 (izrazeno neurolepticko dejstvo)

Grupa 2 (izrazeno ekstrapirimidalno dejstvo)

Grupa 3 (izrazeno antiholinergicko dejstvo)

- Hlorpromazin - Levopromazin- Promazin

- Perfenazin- Flufenazin

- Tioridazinwww.belimantil.info

Butirofenoni

Ostali neuroleptici

Tioksanteni- Klopentiksol -Flupentiksol- Hlorprotiksen

- Droperidol- Haloperidol

- Litijum

- Klozapin

Stabilizatori raspolozenja

**Psihostimulansi**Kortikalni Medularni

-Metilksantini

( Kofein, Teofilin, Teobromin)

- Amfetamin - Inhibitori MAO

- Pentazol

www.belimantil.info

**Barbiturati**Intravenski anestetici

Lekovi protiv epilepsije

- Fenobarbiton-Na

- Tiopenton-Na

- Fenobarbiton

**Miorelaksansi**Depolarizujuci miorelaksansi

Nedepolarizujuci miorelaksansi

- Vekuronijum

- Sukcinil-holin

- Pankuronijum

- Galamin- Atrakurijum

- Rokuronijum

www.belimantil.info

**Anestetici**

Lokalni anestetici

Intravenski anestetici

Inhalacioni anestetici- Halotan - Enfluran - Izofluran - Metoksifluran

- Desfluran - Sevofluran - Azot-suboksid (azotni oksidul)

- Tiopenton-Na - Ketamin - Pentobarbiton-Na

- Propofol- Etomidat -Midazolam

Amidnog tipa

Estarskog tipa

- Lidokain - Mepivakain - Bupivakain

- Prokain - Tetrakain - Kokain - Benzokain

www.belimantil.info

**Opioidni analgetici**

Alkaloidi opijuma i polusintetske zamene

Sintetske zamene za morfin

- Morfin - Kodein - Heroin

- Meperidin - Metadon - Fentanil - Pentazocin - Tramadol

- NaloksonMorfinski antagonisti - Naltrekson

**Antipireticki analgetici**Derivati salicilne kiseline

Pirazoloni

- Acetil salicilna kiselina - Salicilamid- Na-salicilat

- Aminofenazon - Noraminofenazon-metamizol (analgin, novalgetol)

- Paracetamol

Derivati para-amino fenola- Fenacetin

www.belimantil.info

**NSAIL**Selektivni i specificni COX-2 inhibitori

Derivati propionske kiseline

Derivati sircetne kiseline

Derivati oksikama

Derivati pirazolona

Antireumatici drugog reda

- Meloksikam -Etodolak

- Ibuprofen -Naproksen -Flurbiprofen

- Piroksikam -Tenoksikam -Meloksikam

- Diklofenak -Etodolak -Indometacin

- Azapropazon -Fenilbutazon

- Hlorohin -Soli zlata -Imunosupresivi -TNF blokatori

- Celekoksib -Rofekoksib

www.belimantil.info

**Th Epilepsije**1) Fenitoin

2) Karbamazepin

4)Valproinska kiselina

3) Fenobarbiton

5) Oksazolidini (Primetadion i Parametadion)

6) Sukcinimidi (Etosukcimid)

8) Inhibitori ugljene anhidraze (Sultiam, Acetazolamid)

9) Vigabatrin

7) Benzodiazepini (Diazepam, Lorazepam, Klonazepam, Nitrazepam)

- Kortikotropin i Prednizon

Th kod decijih spazama :

- Klonazepam i Nitrazepam

- Diazepam IV (po 1 mg do 30)

Th epi statusa

- Lorazepam (sporo iv infuz)

- Fenobarbiton IV (100, 200,

400 do 800 mg )

- Opsta anestezija

www.belimantil.info

**Th Parkinsonizma**1) Levo-dopa

2) Antiholinergici (Triheksifenidil, Etilbenzatropin, Biperidin)

3) Bromokriptin

5) Amantadin

6) Selegilin

4) Pergolid

www.belimantil.info

CNS Pharmacology

GABA

Synthesis and inactivation Isoniazid GABA

Synthesis Inhibits glutamate decarboxylase originally used for TB

Vigabatrin GABA Degradation

Inhibits GABA transaminase (GABA succinate semialdehyde)

Sodium Valproate GABA Degradation

Inhibits succinate semialdehyde dehydrogenase (succinate semialdehyde succinate)

Tiagabine GABA Reuptake Inhibits the GABA Na cotransporter

GABAA receptor (pentameric heteromer, Cl channel inhibitory) GABA Endogenous agonist Muscimol Agonist Bicuculline Antagonist competitive Picrotoxin Antagonist ion channel block Benzodiazepines Allosteric modulator binds preferentially

between and 2 subunits Barbiturates Allosteric modulator Neurosteroids Allosteric modulator carbolines Allosteric modulator General anaesthetic Allosteric modulator

GABAB receptor (GPCR - gi open K channel,block VGCC, bicuculline insens ) GABA Endogenous agonist Baclofen Agonist anti spasmodic in spinal cord Gamma hydroxyl butyrate Agonist date rape Phaclofen Antagonist 2-hydroxysaclofen Antagonist

Anxiety and GABA Buspirone 5 HT 1A partial

agonist ? feedback inhibitory effect

blockers Somatic anxiety by removing peripheral effects

Tricyclics and SSRI

Antidepressants ? overlap between chronic anxiety and depression

Barbiturates Allosteric activators GABAA

At high [ ] can open channel in absence of GABA. Low TI, tolerance due to hepatic enzyme induction, profound depression and dependence. Largely replaced by BZD but still used as anticonvulsant. Increase channel open time.

Benzodiazepine Allosteric activators

Safer higher TI. Only potentiates the action of released GABA. Increases

www.belimantil.info

GABAA frequency of opening and increases affinity for GABA. BUT dependence, hypnotic, tolerance (due to subunit change) and synergistic with alcohol and anti histamine. Some have long lived metabolites e.g. nordiazepam t1/2 = 60hr. Hang over (effects: anxiolytic, anticonvulsant, hypnotic, muscle relaxant)

Diazepam chlordiazepoxide

Benzodiazepine Anxiolytic long t1/2 metabolised to nordiazepam = hang over.

Nitrazepam Benzodiazepine Hypnotic short t1/2 wears off before am. Zaleplan Acts at BZD site short t1/2. Shows selectivity for 1 unit

(shown to be involved with hypnotic effect) hence without anxiolytic effects. (thought to be due to 2unit)

Flumazenil Antagonist at the BZD binding site on GABAA receptor.

Neurosteroids Allosteric modulator

Includes progesterone metabolites and dehydroxycorticosterone. Enhance agonist binding and Cl flux by increasing frequency of opening. May be able to open channel in absence of agonist.

carboline carboxylate

carboline Allosteric modulator

Inverse agonist at BZD site. Decreases frequency of opening and affinity for GABA.

Glycine (Spinal cord inhibitory [renshaw cell] pentameric receptor) Strychnine Competitive antagonist of glycine receptor. NOT

active at glycine site on NMDA receptor.

Glutamate

Reuptake Dihydrokainate Inhibits neuronal Na dependent uptake SITS Inhibits glial Na dependent uptake.

Ionotropic receptors AMPA (GluR A,B,C,D pentamer. Flip-flop, Q/R RNA editing GluRB) AMPA Selective agonist

Kainate (GluR5-7 KA1-2 pentamer. RNA editing, rapid desensitisation Kainate Selective agonist

NMDA (NR1(alternative splice) + NR2A,B,C,D. sites: glycine (+), pH (low - ), ion channel (Mg), redox (SH ^freq), Zn (-), polyamine (+/-), steroid (+) N methyl D aspartate Selective agonist Dizolcipine Antagonist Ketamine Antagonist (channel block)

www.belimantil.info

Magnesium Antagonist (channel block) Phenylcyclidine Antagonist angel dust! Glycine Co-agonist Dichlorokynurenate Antagonist at glycine site

Anticonvulsants Phenobarbitone GABAA modulator

(barbiturate) Suppress focus, against all but absence. Sedation and tolerance (hepatic enzyme induction) charged not easy to cross BBB

Diazepam GABAA modulator (benzodiazepine)

Suppress spread (less on focus) status epilepticus. Sedation and tolerance (subunit change)

Clonazepam GABAA modulator (benzodiazepine)

Suppress spread (less on focus) status epilepticus and tonic/clonic.

Tiagabine GABAA Reuptake Inhibits GAT-1 Involved in Na dependent uptake. Adjunctive in partials

Vigabatrin GABA inactivation Inhibits GABA transaminase (GABA SSA) Adjunctive in partials

Valproate GABA inactivation Inhibits SSADH (SSA succinate) AND Na channels. Hence increasing GABA and decreasing Na (synergistic effects). All types INCLUDING absence (other anticonvulsants may be contraindicative of absence. Also no sedation so useful for children, because cant afford to sedate children continuously affect learning

Carbamazepine Use dependent Na blockers

Prevent spread. Partials and tonic/clonic

Phenytoin Use dependent Na blockers

Prevent spread. All except absence. Metabolism saturation so need to increment dose slowly and titrate plasma to monitor concentration

Lamotrigine Use dependent Na blockers

Prevent spread. Partials and tonic/clonic

Valproate Use dependent Na blockers

Prevent spread. All types including absence. Useful for children. see above

Ethosuximide T type calcium channel blockers

Absence first line treatment

Trimethadione T type calcium channel blockers

Absence first line treatment

Gabapentin Calcium channel blockers

Adjunct to partials. Sedation. Role in pain can overdose

Levetiracetam N type calcium channel blockers

Adjunct to partials. ? effect on AMPA/Kainate

Flebamate Glutamate receptors

NMDA glycine site.

www.belimantil.info

Levetiracetam Glutamate receptors

AMPA and Kainate receptors. Partials and tonic/clonic.

Absence seizures Valproate Block VG Na channel Ethosuxamide, trimethadione Block T type Ca channel Lamotrigine Block VG Na channel and neuronal

Ca channel Levetiracetam N type Ca channel Carbamazepine, tiagabine, vigabatrin Contraindicated and enhance

absence seizures.

Cerebrovascular accident ischaemic damage. (save the penumbra!!) Drugs used Statins, ACEi, Low dose aspirin, anti inflammatory Future NMDA-R block (dizolcipine side effects) newer tolerated ones

like DEXTROMETHORPHAN. Zn chelators, free radical scavengers, anti-inflammatory, adenosine agonists, combined AMPA/NMDA block, ?synergy between NMDA-R block and antiapoptotic drugs.

Alzheimers disease (B amyloid plaques and neurofibrillary tangles due to hyperphosphorylated tau. Role of secretins in misprocessin of APP) Putative drugs for B amyloid generation

B secretase inhibition (b secretase KO is not harmful) B amyloid vaccination (caused brain inflammation in trials) anti-inflammatory (ibuprofen reduces plaque in a mouse model) plaque solubilisation/inhibition of formation cholesterol lowering agents

Tacrine, dunazepil, rivastigmine

AChE inhibitors, in line with the cholinergic hypothesis But weak effect for 12-24 months maimum.

DOPAMINE

Synthesis and inactivation Carbidopa and benserazide DOPA decarboxylase inhibition (note

all L aromatic aa are substrates at this enzyme trypyophan and histidine.)

Clorgyline, Selegiline MAO A and B inhibitors selectively at low concentration

Reserpine Blocks synaptic vesicle uptake of DA Amphetamine Promotes emptying of vesicles

increasing [DA]I thus decreasing efficiency of uptake process.

Cocaine, nomifensine, benztropine, amphetamine

Block Na DA cotransporter, raising DA t1/2 in extracellular space.

Dopamine receptors. D1 = gs D2 = gi Dopamine D1A < D1B

D2A > D2B Agonist

www.belimantil.info

Quinpirole D2A > D2B Agonist Flupenthixol Non selective Antagonist Sulpiride Non selective D2 Antagonist (atypical) Clozapine C>A=B Antagonist (atypical) Haloperidol A=C>B Antagonist (typical) Spiperone A=C>B Antagonist (typical)

Parkinsons Disease L-DOPA With carbidopa (save for brain) and Domperidone

(antagonise CTZ DA receptors). After 5-10yrs side effects 80% dyskinesias, choreiform movements, 60% decreased efficacy of drug, rapid on/off, psychosis/hallucinations (^DA in mesolimbic system) Because therapeutic window decreases (supersensitivity and more neurones dying) L-DOPA holidays may help. Now aim is to delay L-DOPA use.

Benztropine Muscarinic cholinergic antagonist dry mouth, constipation, blurred vision. 1st line treatment. BUT will exacerbate alzheimers symptoms pro-dementia

Sellegeline MAO-B inhibitor no cheese reaction. Delays requirement for L-DOPA for 1 year and may supplement it to allow a reduced dose.

bromocriptine, lisuride, pergolide

Dopamine agonists. May be used as an adjunct to L-DOPA. Reduces off time but may have more serious side effects than L-DOPA.

Entacapone, tolcopone

COMT inhibitor.

Domperidone Block peripheral DA receptors in the ChemoTrigger Zone. Adenosine A2A antagonist

Reduce activity of indirect pathway, decrease ACh activity, decrease cortical striatal input. No rapid on-off, no dyskinesias, synergistic with L-DOPA allowing reduced dose and prolonging onset of side effects.

Future Antioxidants, glutamate antagonists, glial derived neurotrophic factor (? Neurones simply dormant not dead), transplants.

Schizophrenia Chlorpromazine Fluphenazine Haloperidol Flupenthixol

A>B=C Antagonist

TYPICALS

Typical. Little effect on symptoms. 90% improve (60% on placebo) BUT side effects motor disturbance (D2A) and tardive dyskinesia (involuntary face and trunk movements) Reduce aggression apathy plus loss of emotion. Sedation (H1 block) Postural hypotension (1 block). Breast development and lactation (loss of inhibition by TI DA) and side effects of mACh block dry mouth, constipation and blurred vision. Shows how dirty drugs are.

Clozapine Sulpiride

A

Olanzapine Pimozide

ATYPICALS work. [Clozapine may cause agranulocytosis in ~1% of pt, therefore continuous wbc monitoring must be conducted, making the drug expensive and thus use is limited.

Clozapine, olanzapine Risperidone

5-HT2C inverse agonist; D2 antagonist

The realisation that inverse agonism had an effect to increase firing of VTA and thus has been found to increase DA in PFC and hence decreasing negative symptoms. Note, typicals are only 5-HT antagonists so the increase in VTA firing is less.

Clozapine [Typical + idazoxan]

D2 antagonist and 2 block

Also shown that 2 block may have and effect. Shown to reduce negative symptoms. Shows how clozapine is dirty!

Serotonin

5-HT1A (gi Raphe presynaptic inhibition) Buspirone Agonist (anxiolytic) partial Pindolol Antagonist

5-HT1B (gi presynaptic inhibition) Methysergide Agonist Pindolol Antagonist

5-HT1C (gi alters blood vessel diameter of brain) Sumatriptan Agonist (migrane therapy) Spiperone Antagonist

5-HT2A B C (gq excitation) (c-thought to excite GABA interneurones - VTA) -methyl-5-HT Agonist Ketanserin Antagonist

5-HT3 (ion channel depolarisation) Biguanides Agonist Ondansetron Antagonist (+chemo antiemetic)

DEPRESSION Phenelzine tranylcypromine

MAOi Non selective, irreversible. Thus cheese effect. Also must be careful because MAO ~2-3 weeks to be resynthesised thus if give drugs requiring ^ MAO activity can lead to fatal hypertension.

Moclobemide MAOAi Selective. No cheese effect since B still active. Reversible so other drugs can be administered immediately.

Imipramine, amytriptiline

Tricyclics Inhibit NA and 5-HT uptake. Dirty, having effects at other receptors 1, 2, H1 (block sedation), mACh (block dry mouth)

Nomifensine NA SRI

www.belimantil.info

Citalopram fluoxetine

SSRI Highly specific, long t1/2 3 weeks to Css. Nausea side effect (^5-HT in gut) overdose non lethal, efficacy in ~60%.

Mianserin Not fully understood. No action on monoamine uptake. 2 block (? ^NA by blocking autoreceptors) H1 block (sedation) 5-HT2A 5-HT2C block.

Iprindole Evidence against monoamine theory no effect on MA. Unknown mechanism, no sedation and may not be very efficacious

FUTURE Substance P antagonist failed at phase III CRH antagonist - ? implicated in stress induced depression. In phase III

Manic phases of depression (15% suicide so must be controlled) Lithium Inhibits IMP phosphatase Valproate Inositol uptake inhibition. Anticonvulsant Carbamezepine Anticonvulsant Lamotrigine Anticonvulsant Anti pshychotics

www.belimantil.info

==KVS==**Inotropni lekovi**

Kardiotonicni glikozidi (digitalis)

Beta agonisti

- Digoksin - Digitoksin

- Dopamin - Dobutamin

**Diuretici**Pravi diuretici

Diuretici sa brzim i snaznim dejstvom

- Furosemid - Torasemid - Bumetanid - Piretanid - Etakrinska kiselina

www.belimantil.info

Osmotski diuretici

Diuretici koji stede kalijum

Inhibitori ugljene anhidraze

Ostali diuretici

Diuretici umerene jacine (tiazidi)

- Hlorotiazid - Hidrohlorotiazid - Politiazid

- Bendroflumetiazid - Ciklopentiazid

- Amilorid

- Antagonisti aldosterona (Spironolakton, Proreron)

- Triamteren

- Acetazolamid

- Amonijum hlorid - Preparati zive

- Indapamid

- Diazoksid

antihipertenzivi

- Manitol - Urea - Glicerol

www.belimantil.info

**Vazodilatatori**Organski nitrati i nitriti

Sintetske zamene za NTG

- Nitroglicerol (gliceril-tri-nitrat) - Izosorbid mononitrat

- Pentaeritril tetranitrat - Natrijum nitrit - Pentanol nitrit

- Dipiridamol - Molsidomin

- Izosorbid dinitrat

**Th hipertenzije**Diuretici- Tiazidi (najvise Hlorotiazid)

www.belimantil.info

Antiadrenergicki lekovi

Direktni vazodilatatori

ACE inhibitori

- Hidralazin - Dihidralazin - Diazoksid - Minoksidil

- Na-nitroprusid - Ca-antagonisti

- Kaptopril - Enalapril - Lizinopril - Ramipril

- Fosinopril - Kvinapril - Cilazapril

- Alfa metil dopa - Klonidin - Rezerpin - Beta blokatori

- Blokatori adrenergickog neurona (Gvanetidin, Betanidin, Gvanoksan)

- Gangliski blokatori - retko

- Alfa blokatori (dihidroergotamin/toxin, prazosin, labetalol)

****Antagonisti angiotenzinskih receptoraCentralni antihipertenzivi

- Losartan - Valsartan

- Klonidin- Metildopa - Moksonidin

Jos treba napomenuti : ****

www.belimantil.info

**Antiaritmici**Stabilizatori celiske membrane

Adrenergicki beta blokatori

Lekovi koji produzuju akcioni potencijal

Antagonisti kalcijuma

- Hinidin

- Prokain amid

- Dizopiramid

- Lidokain

- Fenitoin

- Meksiletin

- Tokainid

- Flekainid

- Enkainid

- Propafenon

- Lorkainid

- Propranolol - Esmolol

- Bretilijum - Sotalol - Amjodaron

- Verapamil - Diltiazem - Nifedipin

**Th hiperlipoproteinemije**- Nikotinska kiselina (niacin)

- Fibrati ( Gamfibrozil, Klofibrat, Fenofibrat, Bezafibrat, Ciprofibrat)

- Statini (Fulvastatin, Pravastatin, Atorvastatin, Simvastatin, Lovastatin)

- Holestiramin i Holestipol

www.belimantil.info

ANTIARITMICI

Lekovi male terapijske irine, i sami su aritmogeni i daju se samo u ozbiljnim aritmijama koje moguda ugroze ivot.Ritam srca zavisi od stanja jonskih kanala (Na, Ca, K), kao i funkcije autonomnog nervnog sistema.U SA i AV voru glavni depolariui kon je Ca+, repolariui je K+, a u His-Purkinjeovim vlaknimaNa+.Mehanizmi nastanka aritmija:

1. Poremeaj stvaranja ritma.2. Poremeaj sprovoenja ritma.

a. Odloena naknadna depolarizacijab. Reentry objasniu ti.c. Stvaranje nenormalne pacemakerske aktivnosti (ishemija + poveana adrenergika

aktivnost).d. Srani blok (zbog povrede sprovodnog sistema)

Aritmije koje se lee su one koje stvaraju hemodinamske probleme i one koje ugroavaju ivot. To su:1. Atrijalna tahikardija, flater i fibrilacija.2. Supraventrikularne (AV) tahikardije (reentry u visini AV vora).3. Ventrikularna tahikardija moe da pree u flater i fibrilaciju.

ANTIARITMICI

I klasa Blokatori Na+ kanala grupa lokalnih anestetika.Blokiraju voltano zavisne Na+ kanale u Purkinjeovim vlaknima i miokardu.

Ia podgrupa: HINIDIN i slini lekovi deluju i na atrijalne i na ventrikularne aritmije.Ib podgrupa: LIDOKAIN i sl. deluju na ventrikularne aritmijeIc podgrupa: FLEKAINID i sl. deluju na ventrikularne aritmije.

II klasa blokatori ESMOLOL, PROPRANOLOL

III klasa Blokatori K+ kanala SOTALOL, AMIODARON najbolji su.

IV klasa Antagonisti Ca+ DILTIAZEM I VERAPAMIL

V klasa Meovita grupa DIGITALIS, ADENOZIN, K+, Mg+.

www.belimantil.info

I KLASA

Ia GRUPA hinidin, prokainamid, dizopiramidMehanizam delovanja i farmakoloki efekti. Blokiraju Na+ kanale onda kada su oni otvoreni iliinaktivirani, ali ne i kada su potpuno repolarizovani, tj. zatvoreni blokiraju ih samo kada rade. Timese postie selektivnost samo na one delove tkiva gde se stvaraju aritmije, na ono tkivo koje jedelimino depolarizovano ishemino tkivo i ono koje ima kratku repolarizaciju, kao u tahikardiji. Nanormalno tkivo, tj. normalnu frekvencu srca ne ometaju.Smanjuju nagib depolarizacije i 4. faze akcionog potencijala to dovodi do irenja AP i poveanjarelativnog refrakatarnog perioda.Takoe, dovode do irenja QT intervala.Imaju i antimuskarinske efekte (dizopiramid).Neeljeni efekti. Male su terapijske irine, toksini su na:

1. Kardiovaskularni sistem negativno inotropno dejstvo.2. CNS tinitus, glavobolje.

Cinhonizam trovanje hinidinom.3. Veoma proiren i bifazan QRS kompleks Torsade des Pointes4. Sistemski prokainamid sistemski lupus.

Indikacije. Daju se i za atrijalne i za ventrikularne poremeaje ritma.Interakcije. Sa kardiotoninim glikozidima nikako davati. Hiperkaliemija potencira toksinost ovegrupe lekova.

Ib GRUPA lidokainDaje se samo intravenski i intrahospitalno.Mehanizam delovanja i farmakoloki efekti. Najselektivniji je za Na+ kanale (u otvorenom stanju) uisheminom tkivu od svih antiaritmika. Zbog toga se daje u infarktu, a ne deluje na zdravo tkivo.Najvie deluje na depolarizaciju, uglavnom ne menja irinu AP i QT intervala, kao i refraktarni period.Neeljeni efekti. Manje je toksian za srce od Ia, ali je toksian za CNS. Hiperkalijemija poveavatoksinost.Indikacije. 1) Infarkt miokarda ventrikularne aritmije.

2) Aritmije usled trovanja digitalisom.Spadaju jo i mexiletin, tokainid i fenitoin.

Ic GRUPA flekainid, enkainid, propafenonDeluju na iste faze AP kao i Ia, ali je najmanje selektivan za Na+ kanale pa su najvie aritmogeni.Najopasniji su jer mogu izazvati naprasnu sranu smrt, naroito posle infarkta miokarda.Propafenon je noviji, moe se davati i u trudnoi.Indikacije. Daju se samo onda kad se aritmije ne mogu izleiti drugim lekovima:

1) Ventrikularna tahikardija koja preti da pree u fibrilaciju.

www.belimantil.info

II KLASA blokatori propranolol, esmolol, metoprololMehanizam delovanja i farmakoloki efekti. Simpatika stimulacija poveava nadraljivost srca,sprovodljivost i ulazak Ca+ u eliju. U ishemiji uvek postoji poveana aktivnost simpatikusa i ulazakCa+ to moe da dovede do ventrikularnih aritmija.Primenom -blokatora sve to se spreava. Takoe, oni smanjuju stvaranje cAMP-a to smanjujeulazak Na+ i Ca+ u eliju i sledstvenu depolarizaciju.Na EKG-u produavaju PQ interval.Indikacije. Daju se i za pretkomorske i za komorske aritmije, naroito postinfarktno.

III KLASA blokatori K+ kanala sotalol, amiodaron, bretilijumMehanizam delovanja i farmakoloki efekti. Blokiraju K+ kanale i deluju na fazu repolarizacije,ime produuju srani akcioni potencijal. Takoe, blokiraju i simpatiki sistem (sotalol je i -blokatori ima izraeno negativno inotropno dejstvo), kao i Ca+ kanale.Bretilijum je blokator adrenergikog neurona jer prazni depoe kateholamina.Amiodaron, pored blokade K+ kanala, blokira i Na+ i Ca+ kanale i -receptore. Jedan je od najboljihantiaritmika, a skoro uopte nije proaritmogen, ali je izuzetno toksian na nivou drugih organa:

1. Disfunkcija tireoidne lezde;2. Stvara depozite u koi i ronjai;3. Dovodi do plune fibroze;

Indikacije. Daje se kod refraktarnih aritmija, ali ne dugo. Ako mora due, onda se ugraujepacemaker.

IV KLASA Ca+ blokatori verapamil, diltiazemMehanizam delovanja i farmakoloki efekti. Blokiraju L tip Ca+ kanala u srcu ime smanjujusprovodljivost kroz sprovodni sistem, pa i u AV voru, usled ega dovode do produenja PQ intervala.Indikacije. Za pretkomorske aritmije.Neeljeni efekti. Deluju negativno inotropno na srce i smanjuju minutni volumen.

V KLASA meovita grupa1. Adenozin daje se i.v. u hospitalnim uslovima, deluje veoma kratko (20-30sec). Deluje

na K+ kanale ime hiperpolarie sprovodni sistem. Daje se kod supraventrikularnetahikardije umesto verapamila.

2. Digitalis za atrijalne tahikardije.3. Kalijum za ektopinu aktivnost, ali u viku je tetan jer dovodi do reentry aritmija.4. Magnezijum slian kalijumu, a daje se zajedno sa K+ kod aritmija usled trovanja

digitalisom.

www.belimantil.info

==Respiratorni==**Terapija bronhijalne astme**

1. Adrenergicki Bronhodilatatori

-Salbutamol -Terbutalin -Salmeterol -Fetnoterol

2. Antiholinergici

-Ipratropijum-bromid

3. Metilksantini

-Teofilin -Aminofilin

4. Stabilizatori Mastocita

-Kromolin (natrijum-kromoglikat) -Ketotifen

5. Antagonisti Leukotrijena

-Zileuton -Montelukast -Zafirlukast

6. Glikokortikoidi

-Beklometazon -Budesonid -Flunisolid -Flutikason

www.belimantil.info

**Ekspektoransi**

1. Ekspektoransi koji povecavaju dubinu sonog sloja - mukokinetici

-Voda -Ekspektorantne soli (KJ, NaJ, Bromheksin)

-Ipekakuana -Saponinske droge

2. Ekspektoransi koji menjaju konzistenciju gelnog sloja - mukolitici

-Mukolitici koji kidaju disulfidne veze (Karboksi-cistein, Acetil-cistein)

-Proteoliticki enzimi (tripsin, himotripsin, DNaza, elastaza)

3. Ekspektoransi koji smanjuju adhezivnost gelnog sloja - surfaktanti

-prirodni -polusintetski -sintetski

4. Ekspektoransi koji poboljsavaju aktivnost cilija

-adrenergici (izoprenalin, adrenalin, terbutalin)

-u manjoj meri i prednizon, KJ, aminofilin

www.belimantil.info

**Antitusici**

1. Centralni antitusici

Opijati

-Kodein -Noskapin -Folkodin -Dekstrometorfan

Sintetski centralni antitusici

-Butamirat -Fedrilat -Klofedanol -Pipazetat -Glaucin

2. Periferni antitusici

-Pentoksiverin

-Prenoksidiazin

-Sluzava sredstva (beli zlez)

www.belimantil.info

**Th peptickog ulkusa**Antacidi neutralizatori stvorenog HCl

Mukoprotektivi

- Al(OH)3 , AlPO4

- NaHCO3

- MgO, Mg(OH)2, MgCO3- CaCO3

- Mg-trisilikat

- Sukralfat- Mg-trisilikat

- Karbenoksolon

- Preparati koloidnog bizmuta

- Mizoprostol

Lekovi koji uklanjaju druge faktore

ERADIKACIJA HELICOBACTER PYLORI

- Amoksicilin 500mg 3x1- Metronidazol 400mg 3x1- Omeprazol 20mg 2x1

==GIT==

www.belimantil.info

Inhibitori stvaranja HCl

H2 antihistaminici

Antiholinergici

Inhibitori sekrecije gastrina

Inhibitori protonske pumpe

- Ranitidin - Nizatidin- Famotidin

- Somatostatin - Oktreotid

- Atropin - Skopolamin-butil-bromid - Oksifenciklimin - Pirenzepin

- Omeprazol - Lansoprazol

- Rabeprazol- Pantoprazol

www.belimantil.info

**Antiemetici**

1) Antimuskarinski lekovi

2) H1 antihistaminici

3) Antidopaminski lekovi

4) Antagonisti serotoninskih receptora

5) Piridoksin

6) Kanabinoidi

- Atropin - Skopolamin - Benzatropin

- Difenhidramin - Prometazin - Ciklizin- Buklizin - Meklizin

- Fenotiazini

(hlorpromazin)

- Metoklopramid - Domperidon- Bromoprid - Butirofenoni

(Haloperidol,

Droperidol)

- Ondasetron - Tropisentron - Granisentron

- Vit B6

- TetraHidroKanabinol - Nabilon - Levonantradolwww.belimantil.info

**Emetici**

**Spazmolitici**

**Prokinetici**

- Apomorfin - Ipekakuana- Iritantne soli

(CuSO4, ZnSO4,

Zn-Acetat)

- Drotaverin - Skopolamin-butil-bromid- Mebeverin

- Metoklopramid - Domperidon - Cisaprid

**Antidijaroici**-Opijati (ranije tinctura opii,

sad vise ne)

- Loperamid- Difenokslat

- Bizmut-silikat -Bioloski preparati ( Lyobif, Flonivil BS)

www.belimantil.info

**Laksansi**

Laksansi koji su omeksivaci stolice

Laksansi koji deluju zapreminom

Nadrazajni laksansi

Drugi laksansi koji se jos koriste

- Ricinusovo ulje - Antrahinonske

droge (list sene)

- Bisakodil

- Biljna vlakna

(citrucel, metamucil

- Agar (bozen tablete) - Soni laksansi

(MgSO4, Mg(OH)2,

Na2SO4

- PoliEtilenGlikol

(salinska lavaza

creva)

- Tecni parafin -Dioktil-Na-Sulfosukcinat - Glicerol

- Laktuloza -Cisaprid

www.belimantil.info

Beta-laktamski antibiotici(penicilini, cefalosporini, monobaktami i karbapenemi)

PENICILINI

1. benzilpenicilini i srodni penicilini (prirodn, uskospektralni)-parenteralno

benzilpenicilin(penicilin G)-suvi-kristalni, rastvorljive Na i K solidepo penicilini:prokain-benzilpenicilin (JUGOCILIN) im, benzatin-benzilpenicilin (PANAPEN)im,benzilpenicilin+prokain-benzilpenicilin

-oralnipenicilin V (fenoksimetilpenicilin) CLIACIL

2. penicilini otporni prema penicilinazi (antistafilokokni)oksacilini (oksacilin, kloksacilin, dikloksacilin, nafcilin), meticilin

3. penicilini proirenog spektra dejstva (aminopenicilini, irokospektralni)amoksicilin, ampicilin PENTREXYL, pivampicilin, metampicilin

4. antipseudomonasni (karbenicilini i ureidopenicilini)azocilin, mezocilin, piperacilin PIPRIL, tikarcilin

INHIBITORI BETA-LAKTAMAZAklavulanska kiselina, tazobaktam, sulbaktamkombinovani preparati: AMOKSIKLAV, PANKLAV=kk+amoksicilin,SULTAMICIN=sb+ampicilin,TAZOCIN=tzb+piperacilin

MONOBAKTAMI (aztreonam) I KARBAPENEMI (imipenem)

*Th penicilinskog oka:1.Adr im 1 mg (10g/kg kod dece) ili iv 10 puta manje, ponovljati pp svakih 10-20 min,obicno 4-5 puta2. Antihistaminik iv (prometazin,difenilhidramin,hlorpiramin) potom oralno tokom 48h,3. Aminofilin 250-500 mg iv polako, ako dominira bronhospazam,4. Kortikosteroid im, dejstvo nastupa za 45 min.

CEFALOSPORINIPrva generacija

Cefaleksin PALITREXpos, Cefazolin GALACEF, Cefadroksil DURACEFposDruga generacija

Cefaklor ALFACETpos, Cefamandol MANDOL, Cefoksitin MEFOXIN, CefuroksimNILACEF, ZINACEF, Cefprozil CEFZILpos

Treca generacijaCefotaksim TOLYKAR, CEFAPAN, Ceftriakson LONGACEPH, AZARAN,ROCEPHIN, Cefpodoksim OBRELANpos, Ceftazidim FORTUM, FORCAS,Cefoperazon CEFOBID, Ceftibuten CEDAXpos

etvrta generacijaCefpirom CEFROM, Cefepim MAXIPIME, MAXICEF

www.belimantil.info

OSTALI INHIBITORI SINTEZE EL. ZIDAVankomicin, Teikoplanin, Fosfomicin, Bacitracin, Cikloserin

AMINOGLIKOZIDI prvenstveno za g- bakterijeStreptomicin, Gentamicin GENTAMICIN, GARAMICIN, Amikacin AMIKACIN,Netilmicin NETROMYCIN, Tobramicim TOBREX, Kanamicin,NEODEKSACIN=dexametazon+neomicin

ANTITUBERKULOTICIIzoniaazid IZONIAZID, Rifampicin RIFTAN, RIFAMOR, StreptomicinSTREPTOMISIN-SULFAT inj., Etambutol MYAMBUTOL

LEKOVI PROTIV LEPREDapson, Rifampicin, Klofazimin

Hloramfenikol CHLORAMFENIKOL

TETRACIKLINI per osPrirodni: Tetraciklin AMRACIN, Oksitetraciklin, HlortetraciklinModifikovani: Doksiciklin DOVICIN,VIBRAMICIN, Demeklociklin, Metaciklin

MAKROLIDIEritromicin ERITROMICIN, Azitromicin HEMOMYCIN, Roksitromicin RUNAC,ROXIMISAN, Klaritromicin KLACID, Midekamicin MACROPEN, SpiramicinROVAMICIN, Telitromicin KATEK

LINKOZAMINIKlindamicin KLINDAMICIN, Linkomicin LINCOHEM, LINCOCIN

FUZIDINSKA KISELINA

AB ISKLJUCIVO ZA LOKALNU PRIMENUPolimiksin, Bacitracin, Neomicin, Bacitracin+ Neomicin =BIVACYN

SULFONAMIDI (Antifolati)Sulfagvanidin, Sulfadiazin-srebro SANADERM, Sulfasalazin,Sulfametoksazol+Trimetoprim=Kotrimoksazol BACTRIM, BIOPIRIN, TRIMOSAZOL,TRIMOSUL, BACTIMOL 5-aminosalicilna kiselina 5-ASA

FLUOROHINOLONICiprofloksacin CIPROCINAL, Norfloksacin, Fleroksacin QUINODIS, OfloksacinVISIREN

UROANTISEPTICINitrofurantoin, Metenamin-mandelat, Hinoloni: Nalidiksinska kis, Pipemidna kis,Oksolonska kis.

ANTIGLJIVINI LEKOVI...ANTIVIRUSNI LEKOVI...ANTIMALARICI...AMEBICIDI...ANTIPARAZITNI LEKOVI...

www.belimantil.info

==Antibiotici==**Penicilini**

Prirodni penicilini

Penicilaza rezistentni penicilini

Penicilini prosirenog spektra - Aminopenicilini

Penicilini protiv pseudomonasa

- Benzilpenicilin (penicilin G) par ent

- Benzatin-benzilpenicilin

- Prokain-benzilpenicilin

- Klemizol-benzilpenicilin

- Fenoksipropilpenicilin (propicilin)

- Fenoksimetilpenicilin (penicilin V)

- Feneticilin

- Benzilpenicilin+prokain-

benzilpenicilin (bipenicilin, jugocilin)

per os :

Depo preparati :

- Oksacilin - Kloksacilin - Dikloksacilin - Flukoksacilin

- Ampicilin - Amoksicilin - Pivampicilin - Metampicilin

- Karbenicilin - Karfecilin - Ureidopenicilini :

- Mezlocilin- Azlocilin - Piperacilin

www.belimantil.info

Monobaktami- Aztreonam

Karbapenemi- Imipenem

**Karbapenemi i Monobaktami**

**Glikopeptidi**- Vankomicin - Teikoplanin

**Makrolidi**- Eritromicin - Linkozamini (Linkomicin, Klindamicin)

- Fuzidinska kiselina (stanicid)

- Azitromicin - Klaritromicin

**Streptogramini**- Kvinupristin - Dalfopristin

www.belimantil.info

**Cefalosporini**

Prva generacija

Druga generacija

Treca generacija

Cetvrta generacija

- Cefazolin par ent - Cefaleksin per os

- Cefuroksim par ent - Cefaklor per os

- Cefotaksim par ent - Cefiksim per os

- Ceftriakson par ent

- Ceftazidim par ent

- Cefpirom par ent

- Cefepim par ent

www.belimantil.info

**Aminoglikozidi**- Streptomicin

- Gentamicin

- Tobramicin

- Amikacin

- Neomicin

- Kanamicin

**Tetraciklini**- Tetraciklin

- Oksitetraciklin

- Metaciklin

- Doksiciklin

**Sulfonamidi**- Sulfadiazin (opste infekcije)

- Sulfadimetoksin (depo preparat)

- Sulfacetamid (za lokalnu primenu)

- Sulfafurazol (za mokracne infekcije)

- Sulfagvanidin (za crevne infekcije)

- Salazosulfapiridin (za crevne infekcije)

Kotrimoksazol (baktrim) =

trimetoprim+sulfometoksazol

www.belimantil.info

**Uroantiseptici**1) Nitrofurantoin

2) Metamin-mendelat

3) Hinoloni

Nalidiksinska kiselina

Pipemidinska kiselina

Fluorohinoloni

Ofloksacin

Nofloksacin

Ciprofloksacin

Flourohinoloni trece generacije

- Levofloksacin - Lomefloksacin

**Antibiotici za lokalnu primenu**

- Polimiksin - Bacitracin - Neomicin

www.belimantil.info

**Amebicidi**

Tkivni Luminalni

- Emetin i Dihidroemetin

- Metronidazol

- Hlorokin

- Jodokinol i Kliokinol

- Diloksanid-furoat

- Neki antibiotici :

- Tetraciklini

- Eritromicin

- Paromomicin

**Antituberkulotici**

- Rimfampicin

- Izoniazid

- Etambutol

- Etionamid

- Pirazinamid

Alternativni antituberkulotici :

- Kapreomicin

- Cikloserin

- Para amino salicilat (PAS)

www.belimantil.info

**Antimikotici**

Antimikotici za sistemsku primenu

Antimikotici za lokalnu primenu

- Amfotericin B

- Flucitozin

- Derivati imidazola ( Mikonazol, Ketokonazol)

- Grizeofulvin (zbog teratogenosti i kancerogenosti umesto njega koristimo

Itrakonazol i Terbinafin)

- Flukonazol

- Nistatin

- Tolnaftat

- Derivati imidazola za lokalnu primenu (Mikonazol, Klotrimazol, Tindazol)

- Natamicin

www.belimantil.info

**Antivirusni lekovi**

Lekovi protiv Herpesa

Inhibitori proteaze

Inhibitori reverzne transkriptaze

Ostali- Amantadin - Ribavirin - Interferoni

- Indinavir - Ritonavir

Analozi nukleozida : Ne-nukleozidni inhibitori r.t.

- citidina (Zalcitabin, Lamivudin)

- timidina ( Zidovudin, Stavudin)

- inozina (Didanozin)

- Efavirenz

- Aciklovir

- Ganciklovir

- Famciklovir

- Penciklovir

- Valaciklovir

- Foskarnet

www.belimantil.info

**Antiparazitarni lekovi**

Lekovi protiv skabies-a

Antihelmintici

- Heksahlorcikloheksan

- Benzil-benzoat

- Krotamiton

- Sumpor mast ili alkalni sulfidi

- Albendazol

- Mebendazol

- Niklozamid

- Tiabendazol

- Piperazin

- Pirantel-Pamoat

www.belimantil.info

ANS.pdfCNS.pdfCNSPharmacology.pdfKVS.pdfAntiaritmici.pdfRespiratorni.pdfGIT.pdfAntibiotici.pdfAntibiotici.pdf