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Heart DM
Heart DM
disopyramide
- strong anticholinergic and negative inotropic effect
ajmaline, prajmaline
I.b. Small reduction in phase 0 slope + shorten repolarizatio
On-off: < 1 sec
Use: ventricular arrhytmias
lidocaine
- rapid association and dissociation with inactivated Na+ channels
- ischemia, AMI
- only iv.
- CNS side effects
mexiletine
- oral analog of lidocaine, CNS side effects
phenytoin
- CNS
- enzyme induction
- MM pharmacokinetic
I.c. Pronounced reduction in phase 0 slope, minor effects on the
duration of repolarization
On-off: > 10 sec
Use: supraventricular arrhytmias
propafenone
- β-adrenerg blockade, K+ channel blockade
- GI side effects
flecainide
- Ca2+ channel blocking effect, visual disturbances
moricizine
enkainid
II. class: β-blockers
- symphatic tone↓ (cAMP)
- heart rate ↓
- AV nodal conductance time ↑
- myocardium contractility ↓
Use:
- supraventricular arrhytmias (AV reentry)
- physical, emotional stress
esmolol, propranolol
III. class: K+ channel blockers
- action potential prolongation (repol)
- HERG channels
- reverse use-dependency
- QT: ↑
- QRS: no changes
Use: ischemic ventricular arrhytmias
Toxicity: afterdepolarization
amiodarone
- Na+-, Ca2+ channels, α- and β-rec. blocking effect
- slow absorption, long t1/2
Side effects: corneal microdeposits, GI, liver failure, pulmonary
fibrosis
sotalol
- D-isomer
- no effects on β-adrenerg receptor function
bretylium
- only parenterally
- for ventricular arrhytmias
- antihypertensive
ibutilid
dofetilid
Use: atrial fibrillation
IV. class: Ca2+ blockers
verapamil, diltiazem
- block the cardiac Ca2+ channels in slow-response tissues (sinus,
AV nodes)
- AV-conduction decreases
Use:
- AV reentrant tachycardia
Side effects:
- BP ↓, constipation, nausea
Other antiarrhytmic drugs
adenosine
- activates Ach-sensitive K+ current → hyperpolarization
- cAMP ↓ (Gi)
- short t1/2; bronchospasm
Mg
- iv.
- torsaede de pointes, cardiac glycoside intox., EAD, DAD
cardiac glycosides
- prominent vagtonic actions
- activation of Ach-mediated K+ currents in AV node
- atrial flutter → atrial fibrillation
ivabradine
- If channel blocker → in sinoatrial node
- mixed Na+–K+ inward current
- Use: stable angina pectoris
Principles
Goals:
- life expectancy ↑
- symptoms ↓
- identify and remove precipitating factors
Atrial extrasystole:
- should not be treated
- β-blockers
Attrial flutter:
- propafenone, amiodarone
- verapamil, diltiazem
Atrial fibrillation
-potassium channel blockers
-quinidine, disopyramide
Ventricular arrhytmias
-lidocaine, procainamide (AMI)
-I/b. (cardiac glycoside intoxication)
I. osztály: depolarizációgátlók (Na-csatorna)
I./A.
- K+-csatornát is gátolják, lassú disszociáció (5-30 s)
- QRS-kiszélesedés, proaritmiás hatásúak (QT, ingervezetés gátlása)
- normál frekvencián is hatásosak
disopiramid
- nincs forgalomban
KI:
- megnyúlt QT-táv. és QRS-komplexus
- szívelégtelenség, bradikardia, teljes AV-blokk
- alacsony vérnyomás
Int:
- digoxin szintje nő
- vérnyomáscsökkentő/sinuscsomóra ható szerek
- antikolinerg szerek
- negatív inotróp szerek
- enziminduktorok, -inhibítorok
A: 2x/nap
prajmalin (NEO-GILURYTMAL tbl.)
- gyengébb negatív inotróp hatás, mint a kinidin
Ind: szupraventrikuláris tachycardia
Mh:
- émelygés, étvágytalanság
- fejfájás, hőhullám
- intrahepatikus cholestasis
- vezetési zavarok
KI:
- bradikardiával társult vezetési zavarok
Int:
- szívglikozidok
- hormonok, szulfonamidok, szalicilátok (cholestasis)
I./B.
- főként az inaktív Na+-csatornákhoz kötődnek (τ=0,1-0,4 s)
- K+-csatornát nem befolyásolják
- csak a károsodott, ischémiás szöveten hatnak
- nincs proaritmiás hatásuk
- leállás: 2 hét
III. osztály: késői repolarizáció gátlók
- K+-csatorna gátlók
- nincs negatív inotrop hatásuk
- QT ↑, QRS nem változik
- fordított use-dependencia
amiodaron (CORDARONE tbl., inj.)
- csak inaktív Na+-csatornához kötődik
- bradikardia – atropinnal nem antagonizálható
- nem kompetitív - és β-AR gátló
- perifériás ellenállás ↓→ O2-fogyasztás ↓
Kin:
- jódtartalmú
- lipidoldékony
- t1/2: 40-80 nap
- telítő és fenntartó dózis (per os is)
Ind:
- legtöbb ritmuszavarban alkalmazható, egyik leghatásosabb szer
Mh:
- tüdőfibrózis
- látási zavar (lerakódás a korneában), a bőr kékes-szürkés
elszíneződése
- KIR zavar, fémes ízérzés
- hipo/hipertireoidizmus
- proaritmiás H gyenge
KI:
- pajzsmirigybetegség, jódallergia
- SA- és AV-blokk
Int:
- β-blokkolók/verapamil
- orális antikoagulánsok, szívglikozidok vérszintje nő
sotalol (SOTAHEXAL tbl., SOTALEX MITE tbl.)
- racém! (D-:”tiszta”, L-: béta-blokkoló)
- II. és III. oszt. kombinációja
- nem szelektív β-blokkoló
- nem gátolja a Na+- és a Ca+-csatornákat
Ind:
- szupraventrikuláris aritmiák
- ventrikuláris aritmiák
Mh: β-blokkoló MH-ok és proaritmiás H
A: 160-640 mg (nagyobb, mint antihipertenzívumként)
F: a terápiát fokozatosan kell befejezni!
vernakalant
IV. osztály: Ca-csatorna gátlók:
- sinuscsomó – közvetlen gátlás
- AV-csomó – ingerületvezetés ↓
- frekvenciafüggő
verapamil
diltiazem
Ind: szupraventrikuláris tachikardia
Egyéb:
adenozin (ADENOCOR inj.)
Hm:
- acetilkolion-függő K+-áram ↑ → hiperpolarizál
- cAMP ↓ (Gi) – Ca-áram gátlás
- sinuscsomó és AV-csomó gátlása
Ind: paroxismális supraventrikuláris tachikardia
KI:
- II. v. III. fokú AV-blokk
- asthma, obstruktív légzőszervi betegség
MH: arckipirulás, flush, AV-blokk, pitvari/kamrai extraszisztole
Int: xantinok – antagonizmus
szívre ható szerek
A: gyors iv. bolus inj.
(rövid féléletidő)
Pharmacological treatment of
diabetes mellitus
Regulation of blood sugar level:
HYPOGLYCEMIA: < 3 mmol/l
glucagon injection
- synthetic human glucagon
Therapeutic use: severe hypoglycemia
Effects:
- stimulates the liver to break down glycogen to be released into the
blood as glucose
- activates gluconeogenesis, the conversion of amino acids into glucose
- effect within 10 minutes
- as the patient responds to treatment → oral CH→ refill of glycogen
store in the liver
- if no respond → iv. glucose
Contraindication:
- hypersensitivity
- liver failure, alcoholism
Interaction:
- insulin
- indomethacin
Insulin
Effects:
1. stimulates glucose uptake in the liver, muscle and adipose tissues
storage: glycogen
2. glycogen-synthase ↑ (liver)
3. lipase activity ↓ → fat mobilization ↓
ketone bodies (FFA)
4. gluconeogenesis ↓ (liver, sceletal muscle)
5. K+- uptake ↑ (liver, sceletal muscle, adipose tissues)
6. glycerin production ↑, FFA ↓
7. protein synthesis ↑
Insulin release:
- 40 U/adults − daily requirements
Pharmacokinetics:
- GI: degradation
- hepatic and renal metabolism
- renal excretion
Therapeutic indication:
- DM 1
- DM 2 (if OAD + diet is not enough)
- pregnancy (if diet is not enough)
- preoperative medication and intensive therapy in DM
- emergency treatment of hyperkalaemia
Side effects:
- hypoglycemia and its symptoms
- oedema
- lipoatrophy
- insulin allergy
- insulin resistance: antibodies
Interaction:
- hypoglycemia: ethanol, β-antagonis, ACE-I, fibrates,
sulphonamides
- hyperglycemia: adrenalin, glucocorticoids, thiaside diuretics, β-
agonists, glucagon, GH, sexual streoids, thyroid hormones
Ultra-rapid acting insulins:
- insulin analogs (recombinant, human)
lispro
B28 proline → B29 lysine
aspart
B28 proline → aspartic acid
glulisin
B3 aspartic acid → lysine
B29 lysine → glutaminic acid
- aqueous solution
- faster absorption → ~ 15-20 min (no dimer/hexamer)
- max. effect: within 0,5-1 h
- shorter duration of action → 2-5 h
- neutral pH, small amount of Zn
- important in postprandial insulin level
Advantage:
- no break between the injection and eating
- lower risk of the development of postprandial hyperglycemia
Administration:
- 1-15 minutes before meal
Rapid acting insulin:
regular (crystalline zinc insulin) insulin
- aqueous solution of human insulin (dimer/hexamer)
- sc. and iv. administration
- natural pH, low amount of Zn
- effect within 30 minutes
- max. effect: 1-3 h
- duration of action: 5-8 h
Intermediate-acting insulins:
- in combination with protamine, zinc, phosphate buffer →
suspension of insulin + aqueous solution of insulin → rapid onset
but longer duration of action
- just sc. !! (suspension)
- 9-18 h effects
NPH-insulin = 30% aqueous insulin + 70% isophane insulin
suspension (NPH = neutral protemine Hagedorn)
NPL-insulin = lispro-protamine insulin
25% lispro insulin + 75% lispro insulin protamine suspension
NPA-insulin = crystalline protamine aspartic insulin + aqueous
aspartic insulin
Pharmacological treatment
Insulinotrop agents:
- sulfonylureas
- glinides
Non-insulinotrop agents
- biguanides
- thiazolidinediones
- α-glucosidase inhibitors
Increasing incretin effects:
- DPP-4 inhibitors
- GLP-1 receptor activators
Others:
- SGLT2-inhibitors
Sulfonylureas
Mechanism of action:
- inhibition of ATP-sensitive K+ channel (pancreas cells) (SUR1
subunit)
- insulin secretion ↑ (secretagogues)
- just in the presence of insulin
Indication:
-type 2 DM (no respond to diet)
-can be combined with other OAD
and insulin
glibenclamide
glipizide
gliclazide
glimepiride
Pharmacokinetics:
- good absorption from the GI tract
- strong plasma protein binding
- hepatic metabolism, renal excretion
- short t1/2 : glipizide, gliclazide
- longer t1/2: glibenclamide, glimepiride
- short t1/2, but long effect
- placenta, milk?!
Interaction:
- plasma protein binding (coumarins, NSAID)
- hypoglycemia
- hyperglycemia
Side effects:
- hypoglycemia
- appetite ↑, weight gain
- GI: nausea, vomiting
- allergic skin reaction, photosensitivity
- hematological side effects (BMD)
- liver failure, jaundice
Contraindication:
- pregnancy, breast feeding?
- elderly
- severe liver- and kidney failure
Administration:
- 30 minutes before meal
- long half-life – morning/1x
- short half-life – 2-3x/day
Glinides:
- not so effective as sulfonylureas
- no effect without insulin
- effect on the postprandial glucose level
Mechanism of action:
- KATP channel inhibition
- insulin release ↑ (secretagogues)
Therapeutic uses:
- type 2 DM
- can be combined with metformin
repaglinid tablet
nateglinid tablet
Pharmacokinetics:
- rapid absorption, rapid excretion (4-6 h) → minimal possibility of
hypoglycemia
- t1/2 = 1-1,5 h
- hepatic metabolism
- renal- (nateglinid), bile (repaglinid) excretion
Side effects:
- hypoglycemia (rare)
- abdominal pain, nausea
- allergy
Administration:
- before meal
Contraindication:
- pregnancy, breastfeeding
- liver failure
Biguanides:
metformin tablet
- effective in lack of working β cells
- not stimulate insulin release from the pancreas
- antihyperglycemic, not hypoglycemic
Mechanism of action:
- stimulate AMP-dependent protein-kinase → hepatic glucose
production ↓, ↑ insulin action in muscle and fat
- Absorption of glucose ↓, appetite ↓
Therapeutic uses:
- DM 2. monotherapy or combination (diet)
- PCO + insulin resistance
Pharmacokinetics:
- good oral absorption
- excreted unchanged (kidney)
- short t1/2 → 3X/day
Sise effects:
- GI symptoms: diarrhea, nausea, decreased appetite
- metallic taste
- lactic acidosis
- Vitamin B12 absorption ↓
Contraindication:
- pregnancy, breastfeeding
- liver failure, alcohol (lactic acidosis)
- pulmonary-, heart failure (lactic aacidosis)
- kidney failure
- lactic acidosis
Interaction:
- loop diuretics
- glucocorticoids, sympathomimetic agents
- ethanol
Thiazolidinediones (glitazones):
- increase insulin sensitivity in peripheral tissues
- effective only when insulin is present
pioglitazone tablet
Mechanism of action:
- peroxisome proliferator-activated-γ-receptor agonist (PPARγ)
Effects:
- regulate CH and lipid metabolism
- lower hepatic glucose production
- ↑ glucose transport into muscle and adipose tissue
- activate genes → regulate fatty acid metabolism in peripheral tissue
- regulate fatty acid metabolism in peripheral tissues
- effects after more weeks!
Indication:
- monotherapy if there is no respond to diet + if metformin is
contraindicated
- combination: metformin, sulfonylureas, insulin
Pharmacokinetics:
- good oral absorption
- strong plasma protein binding
- long half-life
- hepatic metabolism
Side effects:
- weight gain, oedema
- fluid retention, heart failure
- no hypoglycemia
- anemia
- hepatic failure
- bone fractures
Contraindication:
- pregnancy, breastfeeding
- liver failure
- heart failure
α-glucosidase inhibitors:
acarbose tablet
Mechanism of action:
-glucoside inhibition absorption of complex CH↓
- no effect on -galactosidase no effect on diary products
- delay stomach movement
Therapeutic uses:
- DM 2. (monotherapy/combination (insulin, SU, metformin))
Side effects: flatulence, diarrhea, abdominal bloating
A: before meal, 3x/day
Contraindication:
- absorption disorders, bowel disorders (inflammation, obstruction)
- pregnancy, breastfeeding, severe kidney failure
DPP-4-inhibitors:
Mechanism of action:
- dipeptidyl-peptidase inhibition → GLP-1, GIP ↑ → insulin
production and release → glucagon ↓
- glucose-dependent effect
sitagliptin tablet
vildagliptin tablet
saxagliptin tablet
alogliptin tablet
linagliptin tablet
Therapeutic uses:
- DM 2. monotherapy (diet, exercise)
- combination: metformin, sulfonylurea, PPARγ-agonist
Kinetics:
- rapid absorption
- t1/2= ~ 10 h → 1X/day
- excreted unchanged (kidey): sitagliptin
- liver metabolism, renal excretion: vildagliptin, saxagliptin, alogliptin,
linagliptin
Side effets:
- pain in the limbs, GI symptoms
- upper respiratory infections are more common
Contraindication:
- pregnancy, breast-feeding
- liver- and kidney failure
GLP-1 receptor activators:
Mechanism of action:
- glucagon-like peptid-1 (GLP-1) receptor agonist
- incretin effect:
- glucose-dependent insulin secretion ↑
- postprandial glucagon release ↓
- slows gastric emptying, appetite ↓
exenatide injection
lixisenatid injection
liraglutide injection
Therapeutic uses:
- DM 2. in combination (metformin, sulfonylurea, thiazolidinedion)
Kinetics:
- peptide → parenteral administration
- renal excretion
Administration:
- 2X or 1X sc., before meal
Side effects:
- nausea, vomiting
- pain at injection site, allergy
Interaction:
- gastric emptying ↓ → other medications earlier (1h)
SGLT2 inhibitors:
dapaglifozin tablet
canaglifozin tablet→ also in combination with metformin
empaglifozin tablet
Mechanism of action:
- selective, reversible sodium-glucose co-transporter 2 (SGLT2)
inhibitor
Pharmacokinetics:
- strong plasma protein binding
- long t1/2
Side effects:
- back pain
- dyslipidaemia