Pharmacology of the heart and cardiovascular system



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Dr. Lenka Katila

For Health-Care Unit, Kemi Polytechnic school

Luleå, 1999-11-28



Pharmacology of the heart and cardiovascular system




Pharmacology of the heart


  • High mortality due to the cardiovascular diseases leads to high interest to treat it

  • Except primary prevention (healthy life style, motion, low-energy food…) is necessary also a good and sufficient therapy and so called secondary prevention, i.e. early therapy of cardiovascular disease and prevention of the complications.

  • Development of the new drugs for this area is really large and every year comes minimally 10 – 20 new products – drugs.


Effects of cardiovascular drugs:

  1. To quality of the hearth muscle – contractility, inothropy

  2. To the hearth rhythmus and frequency – against arhytmias

  3. To the metabolism of the myocard and the quality of the supplementation of the heart with the blood. (Low flow of blood in the coronary arteries is causing f.ex. angina pectoris.




  1. Contractility

  • Function of the heart as a pump

  • Necessary is presence of the Ca2+ in the cells for myocard-contraction

  • Drugs, which are increasing the concentration of the Ca2+ in the cells are increasing the contractility of the myocard (Cardiac failure)

  • They are called cardiotonics (according to the function)or cardioglykosids( according to the chemical structure)

  • They block Na+K+ATPas in the celular membrane of the myocardial cells and so the slow down exchange of Ca2+ and Na+. Intracelular Ca2+concentration increases and myocard contract more powerful

  • They slow down the rhythmus and conduction on the cardiac conduction pathway and may lead to the arhytmias, but on the other hand is used to therapy of some arhytmias – atrial fibrillation.

  • Side effects: vomiting, dizziness, yellow colored vision, disorientation

  • Low concentration of K+ in the blood can lead to easy overdosing, higher to the toxicity and therefore it is necessary to monitorate the level of the cardioglykosids in plasma

  • Typical drugs:

  • Digoxin, Digoxin, Lanacrist, Lanoxin (p.o., i.v.)

  • Medigoxin: Lanitop (p.o.)

  • Digitoxin: Digitrin (p.o.)

  • Oubain: Strophantin G (i.v.)

New cardiotonics, which effect is due to the inhibition of phosphodiestherase we use in the failing of the classics therapy



  • Amrinon: Inocor, Milrinon :Corotrop (i.v.)










Calcium
Natrium


Kalium

Na

K Na


DIG



Calcium

Natrium


Kalium


2. Antiarhytmics, antidysrhytmics
The complex of mistakes in the cardiac conduction pathway (SA, AV., Hiss, LBB, RBB, and Purkynje f.) causes arrhythmia

  • Most often due to the ischemia of myocard, AIM, ion dysbalance, action of some drugs

  • There are 4 main groups of Antiarhytmics

  1. Na –channels blockers on the cellmembrane:

  • Ia

  • Chinidin (Kinidin Duretter, Kinilentin)

  • prokainamid (Apo-procainamide, Procainamid)

  • disopyramid (Dirytmin,Norpace,Durbis)

  • ajmalin (Gilurytmal)

  • prajmalin (Neo-Gilurytmal)

  • detajmil (Tachmacolor)

  • IB

  • Lidocain – Xylocard

  • Mexiletin – Mexitil

  • Tokainid – Tonocard

  • Fenytoin – Epanutin, Phenytoin

  • IC

  • Propafenon – Rytmonorm

  • Flecainid – Tambocor

  • Lorkainid – Remivox




  1. Beta-sympatholytics – protection against abnormal action of the sympaticus and katecholamins ( see chapter autonomic nerves system)




  1. Drugs prolonging the action potential

  • Amiodaron – Cordarone,Sedacoron

  • Bretylium - Bretylate

  • Sotalol – Darob, Sotahexal, Sotalex




  1. Ca-channel blockers

  • Diltiazem – Cardizem, Coramil, Diltelan, Entrydil

  • Verapamil -Isoptin

Side effects: arhytmias, headache, and palpitations


Therapy: monitoring

Benign arhytmias: slow increasing the doses until the arrhythmia is over

Malign arhytmias: immediate quick therapy according to the arrhythmia
Exceptional arhytmias:

Ventricular fibrillation: defibrillation

Bradycardia: Atropine

Supraventricular arhytmias: Chinidin, Verapamil, beta-blockers, digoxin, and adenosine

Ventricular arhytmias: lidocain, mexiletin, Fenytoin, Amiodaron
3. Therapy of angina pectoris (AP)


  • Therapy of the acute attack of AP

  • Prevention of the attacks of AP

They do not have analgesic effect. The pain relief is caused by vasodilatation in the coronary arteries and higher delivery of O2 to the heart.



Acute attack therapy


  • Nitroglycerin –causing vasodilatation in the venous system, but also in the coronary area

  • Application as a sublingual tablet or bucal spray.

  • It should not be swollen and inspired, because than the effect is prolonged.

  • Right after the pain is stopping the tablet should be spited out. This is preventing the development of tachyphylaxi

  • Nitroglycerin is evaporating and the tablets should be kept outside of the heating sources and used just to the expiry date.



Preventive drugs


  1. Nitrates

  • Similar action like Nitroglycerin

  • Isosorbid mononitrat -Monoket,Fem Mono, Ismo,

  • Isosorbiddinitrat-Sorbangil

  • Because of the possible developement of tachyphylaxe, the dosing is mostly big dose in the morning and no evening dose.

  • Side effects: headache




  1. Beta-blockers – not with vasospastic AP and with the signs of cardiac failure

  2. Ca-channels blockers – dilatation of the arterioles


Schema of the therapy AP






Lower venous return to Lower periphery

resistance

the heart

relaxing the contraction


Venous system



Lower workout





4. Antihypertensiva

  • Hypertension – repeatedly measured BP over 160/95 torr

  • 20% of population

  • Serious risk factor for developement of other diseases – AIM, stroke…

  • myocard must work against higher peripheral resistance

Drugs:


  1. drugs regulating the water and ions balance – diuretics

  2. drugs regulating the sympatic action – Beta- blockers

  3. central Antihypertensiva

  4. Alfa-blockers

  5. vasodilatancia

  1. arterial system –dihydralazin, minoxil, Ca- blockers

  2. venous system – nitrates – not for treatement of hypertension

  3. both systems – ACE – inhibitors

Some antihypertensives can cause orthosthatic hypotensim – collapse.


Schema of the antihypertensive therapy









Arterial resistence

Plasma volume



Diuretics


Increase the amount of urine and the amount of K in urine

Decrease of plasma volume and secondary dilatation

Side effects: Loosing of the K, worse glucose tolerance, hyperlipidemia, and hyperurikemia

(Details in the homework)



ACE inhibitors


  • Inhibitors of the renin-angiotensin system through the inhibition of angiotensin converting enzyme.

  • Inactivation of vasodilatation kinins – decrease or peripheral resistance

  • Kaptopril – Capoten,Captopril

  • Enalapril – Renitec

  • Lisinopril – Vivatec

  • Ramipril – Pramace

  • Trandolapril - Gopten

- Blockers



  • Their action is not very clear, probably optimalisation of the cardiac workout

  • Nonselective, without ISA – metiprondol

  • Nonselective, with ISA - Pindolol,(Visken), Sotalol-Darob

  • Selective with ISA – acebutol

  • Selective without ISA – atenolol(tenormin), betaxolol, metoprolol(Seloken)



Ca-channels blockers


  • Through peripheral resistance decrease, myocardial frequence AV conduction

  • Nifedipin, Dilthiazem



Centrally acting antihypertensives


  • Acting directly in the CNS by decreasing the tonus of the symphaticus

  • Alfamethyldopa- Aldomet,Dopagen

  • Klonidin – Catapressan, Haemiton

  • Guanfacin - Estulic

  • Urapidil - Ebrantil

-Blockers



  • for serious types of hypertension

  • prazosin

  • doxazosiln – Alfadil



Drugs effecting the muscular layer of the capillary wall


  • For serious types of hypertension

  • Minoxidil – Loniten

  • Diazoxid ->Hyperstat

  • Natrium nitroprusid – Nipride



Drugs effecting sympaticus and parasympaticus
Autonomic (vegetative) nerve system is participating importantly on the regulation organism´s functions, which are out of the voluntary control.
Schema of the system:

Drugs, which are effecting those systems, are called:



  1. Sympatomimetic d.

  2. Sympatolytic d.

  3. Parasympatomimetic d.– cholinergica

  4. Parasympatholytic d.– anticholinergica

  5. Ganglioplegica



  1. Sympatomimetic drugs




  • Activation of the adrenergic receptors

  • Directly or by releasing NADR from the postganglionic neuron

  • Basically the effect is called alpha () and beta ().

  • 1 effect: vasoconstriction, mydriasis

  • 2 effect: releasing of NADR lead to the decrease of production of cAMP and thus to decrease of NADR relief, so it is a control mechanism

  • 1 effect:  pulse,  contractility of myocard,  consumption of oxygen,  arythmogenity,  metabolisation ( glycogenglucose, feat tissuefeatty acids)

  • 2 effect: contractions of the smooth muscles of bronchi, uterus, intestines and vessels

  • 3 receptors are on the adipocytes and they might be answer to the therapy of obesity


Using of those effects:

  • 1: prolongation of the effect of the local anesthetics, decongestion of the mucous in the nose, increasing of the blood pressure if seriously decreased, mydriasis

  • 2: antihypertensiva

  • 1:rarely – some types of blocks of the cardiac conduction pathway

  • 2: bronchodialatation with asthma, tocolytics – obstetrics


Adrenaline (epinephrine)

  • direct  and  effect

  • impossible to give per oss

  • extremely high  effect on the heart, in the low doses vasodilatation, in the high doses vasoconstriction

  • bronchodilatation

  • increasing glycemia

  •  O2 consumption

  • indication: CPR, antialergicum, additional substance to the local anesthetics

Noradrenaline



  • mostly 1 effect, the effect on the myocard might be different

  • indication: extreme hypotension, rarely with the shock

Dopamine


  • Effect: vasodilatation,  myocard contractility,  cardiac output

  • Indication: sudden renal or cardiovascular failure

Isoprenalin


Ephedrine



  • Gently effect on the bronchi, stimulation of the heart and  peripheral resistance

  • Psychostimulans!!!

Amphetamine

Metamfetamin

Phenmetrazin



  • Psychostimulancia, anorectic

Clonidin


  • 2 effect

  • decreasing the tonus of the sympaticus

  • indication: hypertension, therapy of the morphinist

- Sympatomimetic effect



  • special group of the drugs, which are used in the therapy of asthma for bronchodilatation or as a tocolytics for relaxing the contractions of the uterus

  • mostly inhalation

  • fenoterol – Berotec ( asthma), Partusisten (obstetrics)

  • salbutamol – Ventolin

  • terbutalin – Bricantyl


Sympatolytica

Direct effect – on the receptor

Indirect effect – block neurotransmitters releasing
- Blockers


  • effect: dilatace of the vessels and hypotension

  • indication: arteriosclerosis, benign prostate hyperplasy, rarely as a antihypertensiva

  • prazosin – antihypertensivum

  • alfuzosin, doxazosin – BPH

  • fentolamin – feochromocytom

  • ergometrin, ergotamin, metylergometrin – uterotonika, antimigrenotika

  • dihydroergotamin, antimigrenotikum

  • dihydroergotoxin – arterosclerosis

- blockers



  • block of the  - receptors

  • see the book and homework

Parasympatolytic and cholinergic drugs – see homework


Analgesics

  • Pain is very often symptom of the diseases; it is as well very unpleasant feeling of discomfort, provocation stress at the organism.

  • Some pain can be treated by the solving of the original problem , especially inflammations, but some must be treated by special drugs, called analgesics

  • There are two groups of those drugs according to the pharmacological effect:

  • Narcotic group – Opioids drugs, anodyne

  • Non – narcotic group – analgesics, antipyretics



Opioids


  • All the drugs, which effect is similar as morphine’s effect

  • Opium – drug ( see drug abusing chapter)

Morphine


  • Effects: against cough, pain, diarrhea, breathing depressions, miosis, euphoria, dysforie, developing of tolerance

  • Mostly iv, im, sc, but there are also per oss forms

  • Morphine, Dolcontin, MST Continuous, Vendal retard

Codeine


  • Antitusicum, analgeticum

  • Citodon, Panocod

Petidin – Dolsin, Dolcontral, Petidin

Analgeticum, im. , iv
Piritramid - Dipidolor

Fentanyl, Sufentanyl, Remifentanyl – i.v. i.m. – Very strong Opioids for anesthetic use

Tilidin – Valoron

Buprenorfin – Temgesic


Nalbufin – Nubain


Tramadol – Nobligan, Tiparol, Tradolan
Naloxon – Narcanti, Naloxone, Intrenon – antagonistic effect

Indication: intoxication, diagnostic use in suspicion for morphinism, end of the anesthesia




Non-narcotic analgesics


They can not even in the high dose provoce the narcotic status

Effects:


  • Analgesia

  • Antipyretic effect

  • Intiflogistic effect - prostaglandin and other mediators of the inflammation

Acetylsalicylic acid



  • Used over 100 years

  • Another effect: antiagregans – against aggregation of the platelets

  • Negative effect to the gastric mucous – irritations, bleeding

  • Can provoke allergic reaction

  • Can provoke Rey syndrome at the neonates, who has the metabolism disturbances

  • Albyl, Barnalbyl per os, tbl., effervescent tbl, Magnecyl, Dispryl, Aspirin



Acetaminophein – Paracetamol


  • Low antiinflamational effect

  • Mostly antipyretic and analgeticum

  • Good tolerance at the GIT and no risk for Rey sy

  • Panadol, Alvedon, Panodil, Citodon, Panocod



Chynin


  • Antimalarikum

  • Rarely as a analgeticum



Analgesics mixtures


  • Mostly several types of the analgesics

  • T.ex. Coldrex, , Alka-Seltzer,Magnecyl-Cofein,…


Ibuprofen


  • Gently for the stomach

  • Strong antiinflamatory effect

  • Brufen, Ibuprofen, Ipren, Ibutop,…

Cells




Special pharmacology

Dr. Lenka Katila

For Health-Care Unit, Kemi Polytechnic,

Luleå, 1999-11-28




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