NEET MDS Lessons
Pharmacology
Antiarrhythmic Drugs
Cardiac Arrhythmias
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity)
– Conduction (conductivity)
– Both
MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm
ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse
Types of Arrhythmias
• Sinus arrhythmias
– Usually significant only
– if they are severe or prolonged
• Atrial arrhythmias
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart
• Nodal arrhythmias
– May involve tachycardia and increased workload of the heart or bradycardia from heart block
• Ventricular arrhythmias
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation
|
Class |
Action |
Drugs |
|
I |
Sodium Channel Blockade |
|
|
IA |
Prolong repolarization |
Quinidine, procainamide, disopyramide |
|
IB |
Shorten repolarization |
Lidocaine, mexiletine, tocainide, phenytoin |
|
IC |
Little effect on repolarization |
Encainide, flecainide, propafenone |
|
II |
Beta-Adrenergic Blockade |
Propanolol, esmolol, acebutolol, l-sotalol |
|
III |
Prolong Repolarization (Potassium Channel Blockade; Other) |
Ibutilide, dofetilide, sotalol (d,l), amiodarone, bretylium |
|
IV |
Calcium Channel Blockade |
Verapamil, diltiazem, bepridil |
|
Miscellaneous |
Miscellaneous Actions |
Adenosine, digitalis, magnesium |
Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR)
• To maintain NSR after conversion from AF or flutter
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation
• When dangerous arrhythmias occur and may be fatal if not quickly terminated
– For example: ventricular tachycardia may cause cardiac arrest
Mechanism of Action
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers)
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells
Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin
Indications:
infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)
Barbiturates
1. Long-acting. Phenobarbital is used to treat certain types of seizures (see section on antiepileptic drugs).
2. Intermediate-acting. Amobarbital, pentobarbital (occasionally used for sleep), secobarbital.
3. Short-acting. Hexobarbital, methohexital, thiopental—rarely used as IV anesthetics.
Doxycycline
Commonly prescribed for infections and to treat acne. treat urinary tract infections, gum disease, and other bacterial infections such as gonorrhea and chlamydia., as a prophylactic treatment for infection by Bacillus anthracis (anthrax). It is also effective against Yersinia pestis and malaria.
Erythromycin
used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.
Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.
Mechanism of action Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.
Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.
Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine.
Erythromycin's half-life is 1.5 hours.
Side-effects. More serious side-effects, such as reversible deafness are rare. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrosis are some other rare side effects that may occur.
Contraindications Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem)
erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time.
Different Systems of the CNS & their functions
These systems are pathways formed of specific parts of the brain and the neurons connecting them.
They include:
1.The pyramidal system
2.The extrapyramidal system
3.The limbic system
4.The reticular formation
5.The tuberohypophyseal system
The pyramidal system:
It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”.
It is responsible for the regulation of the fine voluntary movements.
The extrapyramidal system:
It also controls the motor functionbut involves areas other than the corticospinal tract.
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system.
The “basal ganglia” constitute an essential part of this system.
Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.
The limbic system:
The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas.
The limbic system is involved in the control of “behavior”& “emotions”.
The reticular formation:
It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards.
It is important in the control of “consciousness” and “wakefulness”.
The tuberohypophyseal system:
It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
Sympatholytics (Antiadrenergic Agents)
PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent
It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension.
It increases the cardiac output and decreases the total peripheral resistance.
It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.
Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.
ERGOT ALKALOIDS
Ergotamine is an important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.
METHYSERGIDE
It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine.
SUMATRIPTAN
It is a potent selective 5-HT 1D receptor agonist used in the treatment of migraine.
PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1 receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.
TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½
DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.
TAMSULOSIN
It is uroselective α1A blocker and has been found effective in improving BPH symptoms.
Other drugs used for erectile dysfunction
Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.