Ultimate Pharmacologist

• Cardiac arrest involves cessation of cardiac mechanical activity as confirmed by absence of signs of circulation (eg, detectable pulse, unresponsiveness, and apnea). PATHOPHYSIOLOGY • Coronary artery disease is the most common finding in adults with cardiac arrest and causes ~80% of sudden cardiac deaths. In pediatric patients, cardiac arrest typically results from respiratory failure or progressive shock. • Two different pathophysiologic conditions are associated with cardiac arrest: ✓ Primary: arterial blood is typically fully oxygenated at the time of arrest. ✓ Secondary: results from respiratory failure in which lack of ventilation leads to severe hypoxemia, hypotension, and cardiac arrest. • Cardiac arrest in adults usually results from arrhythmias. Historically, ventricular fibrillation (VF) and pulseless ventricular tachycardia (PVT) were most common. The incidence of VF in out-of hospital arrests is declining, which is of concern because survival rates are highe

• Arrhythmia is loss of cardiac rhythm, especially irregularity of heartbeat. PATHOPHYSIOLOGY SUPRAVENTRICULAR ARRHYTHMIAS • Common supraventricular tachycardias requiring drug treatment are atrial fibrillation (AF), atrial flutter, and paroxysmal supraventricular tachycardia (PSVT). Other arrhythmias that usually do not require drug therapy are not discussed here (eg,) pemature atrial complexes, sinus arrhythmia, sinus tachycardia). Atrial Fibrillation and Atrial Flutter • AF has extremely rapid (400–600 atrial beats/min) and disorganized atrial activation. There is loss of atrial contraction (atrial kick), and supraventricular impulses penetrate the atrioventricular (AV) conduction system to variable degrees, resulting in irregular ventricular activation and irregularly irregular pulse (120–180 beats/min). • Atrial flutter has rapid (270–330 atrial beats/min) but regular atrial activation. Ventricular response usually has a regular pattern and a pulse of 300 beats/min.

Acute coronary syndromes (ACSs) include all syndromes compatible with acute myocardial ischemia resulting from imbalance between myocardial oxygen demand and supply. • ACSs are classified according to electrocardiographic (ECG) changes into  (1) ST-segment-elevation (STE) myocardial infarction (MI) or (2) non–ST-segmentelevation (NSTE) ACS, which includes NSTE MI and unstable angina (UA). PATHOPHYSIOLOGY  • Endothelial dysfunction, inflammation, and formation of fatty streaks contribute to development of atherosclerotic coronary artery plaques.  • The cause of ACS in more than 90% of patients is rupture, fissuring, or erosion of an unstable atheromatous plaque. A clot forms on top of the ruptured plaque. Exposure of collagen and tissue factor induces platelet adhesion and activation, which promote release of adenosine diphosphate (ADP) and thromboxane A2 from platelets producing vasoconstriction and platelet activation. A change in the conformation of the glycoprot

DNA, RNA, replication, translation, and transcription DNA structure One monomer unit = deoxyribonucleic acid Ø   Composed of a base, a sugar (deoxyribose), and a phosphate Ø   Directionality along the backbone 5’ (phosphate) to 3’ (OH) Double-strand pairing: Ø   Complementary base-matching Ø   Base-matching achieved by H-bonding and geometry (long vs short nucleotides) Ø   Antiparallel (one strand 5’   3’, the other 3’   5’) Helical shape Ø   10.4 nucleotides per turn Ø   Diameter = 2 nm Ø   Both major and minor grooves Ø   Called B-DNA. The helix twist and diameter can also change under dehydrating conditions and methylation to A-DNA and Z-DNA Base-pairing and strand interactions Ø   A, G are long (double ring purines) Ø   C,T are short (single ring pyrimidines) Ø   Need one long and one short nucleotide per pair Ø   C-G have three hydrogen bonds (slightly stronger matching) Ø   A-T have two hydrogen bonds (sli