COENZYME Q10 FOR HEART DISEASE

INTRODUCTION: Coenzyme Q10 (CoQ10) is a vitamin-like substance found in most animal cells. It is an essential component in the cell’s mitochondria for producing energy or ATP. Because the heart requires high levels of ATP, a sufficient level of CoQ10 is essential to that organ.

SOURCES OF CoQ10: Foods richest in this substance are pork, sardines, beef heart, salmon, broccoli, spinach, and nuts. Older adults appear to have an increased need for CoQ10. Reports of the benefits of CoQ10 for treating heart disease began to emerge in the mid-1960s. Subsequent reports have claimed that CoQ10 may possibly be effective for mitochondrial disorders; decreasing the risk of subsequent heart attacks following an MI, hypertension, migraines, or Parkinson’s disease; enhancing the immune system; and preventing blood vessel damage following cardiac bypass surgery. Myocardialinfaction: Hypertention: Immunity

Considerable research has been conducted on this antioxidant. Statins block an enzyme involved in the production of CoQ10, creating a deficiency of the antioxidant in patients taking statin medications.

RELATED;

1.  TRADITIONAL AND COMPLIMENTARY MEDICINES

ACUTE CORONARY SYNDROME AND MYOCARDIAL INFARCTION

INTRODUCTION: Acute coronary syndrome (ACS) is an emergent situation characterized by an acute onset of myocardial ischemia that results in myocardial death, also known as myocardial infarction [MI]) if definitive interventions do not occur promptly. Although the terms coronary occlusion, heart attack, and MI are used synonymously, the preferred term is MI.  In unstable angina, there is reduced blood flow in a coronary artery, often due to rupture of an atherosclerotic plaque, but the artery is not completely occluded. This is an acute situation that is sometimes referred to as pre-infarction angina because the patient will likely have an MI if prompt interventions do not occur.

MYOCARDIAL INFARCTION: In an MI, an area of the myocardium is permanently destroyed, typically because plaque rupture and subsequent thrombus formation result in complete occlusion of the artery.

Vasospasm (sudden constriction or narrowing) of a coronary artery, decreased oxygen supply such as, from acute blood loss, anemia, or low blood pressure, and increased demand for oxygen for example, from a rapid heart rate, thyrotoxicosis, or ingestion of cocaine are other causes of MI.

In each case, a profound imbalance exists between myocardial oxygen supply and demand. An MI may be defined by the type, the location of the injury to the ventricular wall, or by the point in time in the process of infarction (acute, evolving, old).

CLINICAL MANIFESTATIONS: In many cases, the signs and symptoms of MI cannot be distinguished from those of unstable angina, hence, the evolution of the term ACS.

1) Chest pain that occurs suddenly and continues despite rest and medication is the primary presenting symptom.

2) Some patients have prodromal symptoms or a previous diagnosis of coronary artery disease (CAD), but about half report no previous symptoms.

3) Patient may present with a combination of symptoms, including chest pain, shortness of breath, indigestion, nausea, and anxiety.

4) Patient may have cool, pale, and moist skin; heart rate and respiratory rate may be faster than normal. These signs and symptoms, which are caused by stimulation of the sympathetic nervous system, may be present for only a short time or may persist.

ASSESSMENT AND DIAGNOSTIC METHODS: Patient history (description of presenting symptom; history of previous illnesses and family health history, particularly of heart disease). Previous history should also include information about patient’s risk factors for heart disease. Electrocardiography (ECG) within 10 minutes of pain onset or arrival at the emergency department; echocardiography to evaluate ventricular function. Cardiac enzymes and biomarkers (creatine kinase isoenzymes, myoglobin, and troponin).

MEDICAL MANAGEMENT: The goals of medical management are to minimize myocardial damage, preserve myocardial function, and prevent complications such as lethal dysrhythmias and cardiogenic shock. Reperfusion via emergency use of thrombolytic medications or percutaneous coronary intervention (PCI). Reduce myocardial oxygen demand and increase oxygen supply with medications, oxygen administration, and bed rest. Coronary artery bypass or minimally invasive direct coronary artery bypass (MIDCAB).

PHARMACOLOGIC THERAPY: Nitrates (nitroglycerin) to increase oxygen supply. Anticoagulants (aspirin, heparin). Analgesics (morphine sulfate). Angiotensin-converting enzyme (ACE) inhibitors. Beta-blocker initially, and a prescription to continue its use after hospital discharge.

RELATED;

1.  ANGINA PECTORIS  

2.  CONGESTIVE HEART FAILURE

3.  HYPERTENSION

REFERENCES

PHYSIOLOGY OF THE CELL MEMBRANE

 

INTRODUCTION: The cell membrane or plasma membrane surrounds the cytoplasm of living cells, physically separating the intracellular components from the extracellular environment. Fungi, bacteria and plants also have a cell wall in addition, which provides a mechanical support to the cell and precludes the passage of larger molecules.

The cell membrane also plays a role in anchoring the cytoskeleton to provide shape to the cell, and in attaching to the extracellular matrix and other cells to hold them together to form tissues. The cell membrane is selectively permeable and able to regulate what enters and exits the cell, thus facilitating the transport of materials needed for survival.

INTRACELLULAR TRANSIT: The movement of substances across the membrane can be either "passive", occurring without the input of cellular energy, or "active", requiring the cell to expend energy in transporting it. The membrane also maintains the cell potential. The cell membrane thus works as a selective filter that allows only certain things to come inside or go outside the cell. The cell employs a number of transport mechanisms that involve biological membranes: Passive osmosis and diffusion: Some substances (small molecules, ions) such as carbon dioxide (CO₂) and oxygen (O₂), can move across the plasma membrane by diffusion, which is a passive transport process. Because the membrane acts as a barrier for certain molecules and ions, they can occur in different concentrations on the two sides of the membrane. Such a concentration gradient across a semipermeable membrane sets up an osmotic flow for the water. Transmembrane protein channels and transporters: Nutrients, such as sugars or amino acids, must enter the cell, and certain products of metabolism must leave the cell. Such molecules diffuse passively through protein channels such as aquaporins (in the case of water (H₂O)) in facilitated diffusion or are pumped across the membrane by transmembrane transporters.

ENDOCYTOSIS: Endocytosis is the process in which cells absorb molecules by engulfing them. The plasma membrane creates a small deformation inward, called an invagination, in which the substance to be transported is captured. The deformation then pinches off from the membrane on the inside of the cell, creating a vesicle containing the captured substance. Endocytosis is a pathway for internalizing solid particles ("cell eating" or phagocytosis), small molecules and ions ("cell drinking" or pinocytosis), and macromolecules. Endocytosis requires energy and is thus a form of active transport.

EXOCYTOSIS: Just as material can be brought into the cell by invagination and formation of a vesicle, the membrane of a vesicle can be fused with the plasma membrane, extruding its contents to the surrounding medium. This is the process of exocytosis. Exocytosis occurs in various cells to remove undigested residues of substances brought in by endocytosis, to secrete substances such as hormones and enzymes, and to transport a substance completely across a cellular barrier. In the process of exocytosis, the undigested waste-containing food vacuole or the secretory vesicle budded from Golgi apparatus, is first moved by cytoskeleton from the interior of the cell to the surface. The vesicle membrane comes in contact with the plasma membrane. The lipid molecules of the two bilayers rearrange themselves and the two membranes are, thus, fused.  A passage is formed in the fused membrane and the vesicles discharges its contents outside the cell.

REFERENCES;

1.  TISSUES

2.  CELLULAR ORGANELLES

3.  ANATOMY AND PHYSIOLOGY  

REFERENCES

HISTAMINE

INTRODUCTION: Histamine is formed from histidine by decarboxylation, catalysed by histidine decarboxylase. The effects of histamine are; Smooth muscle contraction, enhanced vascular permeability, increased acid secretion are the important actions. So histamine causes fall in blood pressure.

PRODUCTION: The major cells producing histamine are platelets, mast cells and basophils. Certain antigens such as penicillin will elicit IgE antibodies that are fixed on the mast cells. When the next dose of penicillin is injected, it reacts with the antibodies; and degranulation of mast cells takes place. Histamine and slow reacting substance (SRS) are released. This leads to peripheral vasodilatation, fall in blood pressure and anaphylaxis.

ANTIHISTAMINES: These are drugs which block histamine receptors. They are used to control allergic and anaphylactic reactions. The stimulant effect of histamine on gastric acid secretion is by acting on H2 receptors. Hence H2 receptor antagonists are used in the treatment of acid peptic ulcers of stomach.

RELATED;

1. PEPTIC ULCERS  

2. ANTIHISTAMINES

3.  BIOCHEMISTRY

REFERENCES

DIGOXIN

Therapeutic Class: Drug for heart failure

Pharmacologic Class: Cardiac glycoside

ACTIONS AND USES: The primary benefit of digoxin is its ability to increase the contractility or strength of myocardial contraction, a positive inotropic action. Digoxin accomplishes this by inhibiting Na⁺-K⁺ ATPase, the critical enzyme responsible for pumping sodium ions out of the myocardial cell in exchange for potassium ions. As sodium accumulates, calcium ions are released from their storage areas in the cell. The release of calcium ions produces a more forceful contraction of the myocardial fibers. By increasing myocardial contractility, digoxin directly increases cardiac output, thus alleviating symptoms of HF and improving exercise tolerance.

The improved cardiac output results in increased urine production and a desirable reduction in blood volume, relieving distressing symptoms of pulmonary congestion and peripheral edema. In addition to its positive inotropic effect, digoxin affects impulse conduction in the heart. Digoxin has the ability to suppress the sinoatrial (SA) node and slow electrical conduction through the atrioventricular (AV) node. Because of these actions, digoxin is sometimes used to treat dysrhythmias.

ADMINISTRATION ALERTS: Take the apical pulse for 1 full minute, noting rate, rhythm, and quality before administering. If the pulse is below the parameter established by the health care provider (usually 60 beats per minute), withhold the dose and notify the provider. Check for recent serum digoxin level results before administering. If the level is higher than the parameter established by the health care provider (usually 1.8 ng/mL), withhold the dose and notify the provider. Use with caution in geriatric and pediatric patients because these populations may have inadequate renal and hepatic metabolic enzymes. Pregnancy category A.

ADVERSE EFFECTS: The most dangerous adverse effect of digoxin is its ability to create dysrhythmias, particularly in patients who have hypokalemia or impaired renal function. Because diuretics can cause hypokalemia and are often used to treat HF, concurrent use of digoxin and diuretics must be carefully monitored. Other adverse effects of digoxin therapy include nausea, vomiting, fatigue, anorexia, and visual disturbances such as seeing halos, a yellow-green tinge, or blurring. Periodic serum drug levels should be obtained to determine whether the digoxin concentration is within the therapeutic range.

CONTRAINDICATIONS: Patients with AV block or ventricular dysrhythmias unrelated to HF should not receive digoxin because the drug may worsen these conditions. Digoxin should be administered with caution to older adults because these patients experience a higher incidence of adverse effects. Patients with renal impairment should receive lower doses of digoxin, because the drug is excreted by this route. The drug should be used with caution in patients with MI, cor pulmonale, or hypothyroidism. 

INTERACTIONS: Drug–Drug: Digoxin interacts with many drugs. Concurrent use of digoxin with diuretics can cause hypokalemia and increase the risk of dysrhythmias. Use with ACE inhibitors, spironolactone, or potassium supplements can lead to hyperkalemia and reduce the therapeutic action of digoxin. Administration of digoxin with other positive inotropic drugs can cause additive effects on heart contractility. Concurrent use with beta blockers may result in additive bradycardia. Antacids and cholesterol-lowering drugs can decrease the absorption of digoxin. If calcium is administered IV together with digoxin, it can increase the risk of dysrhythmias. Quinidine, verapamil, amiodarone, and alprazolam will decrease the distribution and excretion of digoxin, thus increasing the risk of digoxin toxicity. 

RELATED;

1.  CONGESTIVE CARDIAC FAILURE

2.  HYPERTENTION

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

SHOCK

Introduction: Shock is a clinical state of systemic hypoperfusion, in which there is progressive cardiovascular collapse associated with acute reduction in cardiac output and effective circulating blood volume, which results in hypotension, and organs insufficiency.  

PARAMETERS OF STROKE:  Organ perfusion depends on arterial blood pressure (BP), which in turn depends on cardiac output (CO), peripheral vascular resistance (PVR).  Cardiac output (CO) depends on the following equation  (CO)  =      Stroke Volume    x     Heart rate.   In turn, stroke volume depends on Preload (the amount of blood available to fill the ventricles), and after-load (amount of blood available for ejection from the heart).  Any defect in any of these mentioned factors might result in shock.  [PHYSIOLOGICAL FUNCTIONING OF THE HAERT]

CAUSES AND TYPES OF SHOCK: Shock can be classified into 3 types namely; hypovolemic shock, cardiogenic shock, and distributive shock.  

HYPOVOLEMIC SHOCK: This type is caused by reduced blood volume, reduction in circulating blood volume results in a reduction of the preload which leads to inadequate left ventricular filling.  The reduced preload culminates in decreased cardiac output which leads to widespread tissue hypoperfusion.  

Causes of Hypovolemia:  Hemorrhage, dehydration in cases of vomiting or diarrhoea.  

CARDIOGENIC SHOCK: This is a shock that results from severe depression of cardiac performance, primarily resulting from pump failure of the right or left ventricle.  The most common cause is left ventricular MI, shock occurs when more than 40% of ventricular mass is damaged.  

Causes of cardiogenic shock include;  1)Acute MI occurs if ≥ 40% of ventricular mass are involved.  

2) Ventricle outflow obstruction, e.g., aortic stenosis  

3)  Reduction in cardiac output, e.g. Aortic or mitral regurgitation  

4)  Arrhythmia - Cardiac tamponade (fluid accumulation in pericardial space)  

5)  Tension pneumothorax (gas accumulation in pleural space)  

6)  Massive pulmonary embolism - Severe pulmonary hypertension 

DISTRIBUTIVE SHOCK: Refers to subtypes  of shock caused by profound peripheral vasodilatation despite normal or high cardiac output and characterized by, inadequate perfusion of tissues due to mis-distribution of blood flow, and the blood is not reaching the tissues adequately. 

Causes of Distributive Shock:  Septic shock, anaphylactic shock, neurogenic shock.  Septic Shock usually refers to serious bacterial infections caused by Gram-negative organisms.

Pathogenesis of distributive shock: Cell walls of microorganisms contain endotoxins which activate inflammatory mediators, that induce vasodilatation & increase capillary permeability resulting in reduced cardiac output and presenting with shock. [BACTERIAL TOXINS]. 

Anaphylactic shock:  This is defined as a wide spread vasodilatation and vascular permeability, that results from the widespread allergic reaction to an antigen. This hypersensitivity reaction is life threatening. The pathophysiology is due to re-exposure to antigen, resulting in degradation of  IgE bound  mast cells and basophils.  The released contents of granule lead to vasodilatation, increased vascular permeability, broncho-constriction and increased mucus production  [IMMUNOGLOBULIN]

Neurogenic Shock: Shock that results from the loss of sympathetic tone causing massive vasodilatation in the venous vasculature, venous return to the heart, cardiac output, and the most common aetiology include: spinal cord injury, and severe pain.

Clinical Features of neurogenic shock: Low blood pressure, rapid, weak pulse, low urine output, confusion and CNS disturbance, cold extremities, cyanosis and loss of skin elasticity.  [BLOOD PRESSURE]

Systemic Changes in Shock: All systems are affected, but the net results are: Lungs: Changes in the rate and depth of breathing, metabolic acidosis, which stimulates respiratory centers resulting in hyperventilation and adult respiratory distress syndrome (ARDS).  Kidneys: The secretary function of the kidneys is always disturbed in shock. This is due to the circulatory collapse and hypotension but the secretion of renin may aggravate it by the kidney itself, aldosterone by the adrenal and antidiuretic hormone by the posterior pituitary gland. These hormones are secreted in an attempt to retain fluid and restore the blood volume as a compensatory mechanism.

RELATED;

1.  HEART FAILURE

2.  MEDICAL CONDITIONS

[REFERENCES]

CLASSIFICATION OF DRUGS

CLASSIFICATION OF DRUGS:  Day to day we use various pharmaceutical products and traditional medications to treat various diseases.  With advanced research, there is no single medical condition that has not been investigated on and this makes the drug compilation a heap in the markets.  The question would be; How do clinicians and prescribers distinguish between these drugs such that they dispense the right medications for their patients?  The answer is that every drug has a class where it falls and therefore before the drug is given, there will be a specific class of it correlated with the medical condition the patient is suffering from.  On this page, we are going to look at the most common ways drugs are classified and where necessary, examples will be given.  Before we go on, previously we were talking about the effects of drugs on the human body; also known as pharmacodynamics.  If you were not following us, you can click here to read about dynamics of drugs in the human body.

1.  Depending on the microbes they kill:  Drugs can be classified according to the microbe they treat or kill.  In general, we call such drugs antimicrobial agents.  But because we have many microbes like we have been seeing in medical microbiology, the classification can continue to break down antimicrobial agents into their special targets.  In that respect we can have the subclasses like listed below with their examples;

i)  Antibacterial agents:  These are drugs that act on bacteria and they also have several other subclasses as we be seeing later.  Some of the examples of antibacterial drugs include; Penicillins, aminoglycosides and many others.

ii)  Antiviral agents:  We also have drugs that target viruses and we call the antiviral drugs/agent including those that treat HIV also known as Antiretroviral drugs (ARVs).  I have discussed much about viruses and their effects in microbiology and if you want to read about them, click on the links below.  Filoviruses  Antiviral drugs.  Some of the antiviral drugs we have include but not limited to; Zidovudine, Nevirapine, Acyclovir, Abacavir among others.

iii)  Antiprotozoal:  These are drugs that can act on protozoa microbes such as those that treat plasmodium; Artemether and artesunate, sulfonamides and those that can act against some strains of amoeba like Metronidazole.

iv)  Antifungal agents:  We also have drugs that act against fungal infections including but not limited to; Amphotericin B, Nistatin, Clotrimazole etc.

2.  Depending on their mechanism of action:  Drugs can also be classified depending on the way they interact with the body and or microbes, and this is what we call pharmacodynamics.  I have already discussed pharmacodynamics in my previous discussions and if you want to read more about it, click here.  In order for drugs to work, they have receptors onto which they bind and cause the desired effect.  Those receptors are either in different body systems, on body organs or affecting certain chemical reactions as we are going to see in the examples below.

i) Antimetabolites:  Such drugs, will be acting by blocking certain metabolic pathways in the body or in the organism for example; Salfonamides, DNA synthesis inhibitors, Methotrexate and others.

ii)  Cell wall synthesis inhibitors:  From the microbial point of view, it will be evident that these drugs impair development and production of the bacterial cell wall.  We have classes of drugs here such as penicillin, cephalosporines and vancomycin.

3.  Depending on the disease they treat:  Drugs can as well be classified basing on the disease or infections they treat.  This is one of the most broad way of categorizing drugs because, one single category will encircle many subclasses of drugs.  Some of the examples we can have here are; 1) Antihypertensives, and these are drugs that treat high blood pressure also known as hypertention.

4.  Depending on the chemical composition and structural makeup:  Drugs can also be classified depending on their chemical composition and structural makeup.  This structural classification is good but more complex for non pharmacy professionals and therefore we are going to just briefly look at it.

RELATED;

1.  DYNAMICS OF DRUGS AND THE HUMAN BODY

2.  PENICILLINS

3.  AMINOGLYCOSIDES

4.  FILOVIRUSES

5.  ACYCLOVIR

6.  SALFONAMIDES

7.  METRONIDAZOLE

8.  ARTEMISINI COMBINATION THERAPIES

9.  MEDICAL MICROBIOLOGY

AMINOGLYCOSIDES

 

Objectives of the topic:  By the end of this topic, the reader/medical student will be able to;

1.  Describe aminoglycoside as a class of antibiotics

2.  Identify some of the disease treated by aminoglycosides

Introduction:  The aminoglycosides include  streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others.  They are used most widely in combination with a β-lactam antibiotic in serious infections with gram-negative bacteria, in combination with vancomycin or a β-lactam antibiotic for gram-positive endocarditis, and for treatment of tuberculosis.  

General Properties of Aminoglycosides:  They are water-soluble, stable in solution, and more active at alkaline than at acid pH.  

Mechanism of Action:  The mode of action of streptomycin has been studied far more closely than that of other aminoglycosides, but they probably all act similarly. Aminoglycosides are irreversible inhibitors of protein synthesis, with bactericidal activity.  

Pharmacodynamics:  The initial event is passive diffusion via porin channels across the outer membrane.  Drug is then actively transported across the cell membrane into the cytoplasm by an oxygen-dependent process.  The transmembrane electrochemical gradient supplies the energy for this process, and transport is coupled to a proton pump.  Low extracellular pH and anaerobic conditions inhibit transport by reducing the gradient.  Transport may be enhanced by cell wall-active drugs such as penicillin or vancomycin; this enhancement may be the basis of the synergism of these antibiotics with aminoglycosides.  

Inside the cell, aminoglycosides bind to specific 30S-subunit ribosomal proteins.  Protein synthesis is inhibited by aminoglycosides in at least three ways:  

(1) interference with the initiation complex of peptide formation; 

(2) misreading of mRNA, which causes incorporation of incorrect amino acids into the peptide and results in a nonfunctional or toxic protein; and 

(3) breakup of polysomes into nonfunctional monosomes. These activities occur more or less simultaneously, and the overall effect is irreversible and lethal for the cell.  

Mechanisms of Resistance:  Three principal mechanisms have been established: (1) production of a transferase enzyme or enzymes inactivates the aminoglycoside by adenylylation, acetylation, or phosphorylation.  This is the principal type of resistance encountered clinically.  

(2) There is impaired entry of aminoglycoside into the cell.  This may be genotypic, resulting from mutation or deletion of a porin protein or proteins involved in transport and maintenance of the electrochemical gradient; or phenotypic, such as, resulting from growth conditions under which the oxygen-dependent transport process described above is not functional.  

(3) The receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of a mutation.  

RELATED;

1.  QUINOLONES

2.  PENICILLINS

3.  ANTIMICROBIALDRUG RESISTANCE

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

 

BACTERIAL TOXICOGENIC DIARRHEAS

Bacterial Toxigenic Diarrheas:  Excessive volume, life threatening intestinal electrolyte and fluid secretion also known as diarrhea, occurs in patients with cholera, an intestinal infection by Vibrio cholerae. Certain strains of E. coli are also capable of causing a condition known as "Traveler's diarrhea". 

Pathophysiology:  The secretory state is a result of enterotoxins produced by the bacteria. The mechanisms of action of some of these enterotoxins are well understood at the biochemical level. Cholera toxin activates adenylyl cyclase by causing ADPribosylation of the Gas protein, which stimulates the cyclase. Elevated cAMP levels in turn activate protein kinase A, which opens the luminal CFTR Cl– channel and inhibits the Na+/H+ exchanger by protein phosphorylation. The net result is gross NaCl secretion.  And because where sodium goes, water follow by passive diffusion, this leads to in-flow of excess water from the intestinal tissues to the lumen.

Treatment and management:  Modern, oral treatment of cholera takes advantage of the presence of Na+/glucose cotransport in the intestine, which is not regulated by cAMP and remains fully active in this disease. In this case, the presence of glucose allows uptake of Na+ to replenish body NaCl. Composition of solution for oral treatment of cholera patients is glucose 110 mM, Na+ 99 mM, Cl– 74 mM, HCO3– 29 mM, and K+ 4 mM. The major advantages of this form of therapy are its low cost and ease of administration when compared with intravenous fluid therapy.

RELATED;

1.  DIARRHEA

2.  CONSTIPATION

3.  PATHOGENICITY OF MICROORGANISMS 

REFERENCES