pham exam 5

female productive cycle

The normal reproductive or menstrual cycle is complex sequence in changes of plasma hormone concentration of several hormones and in the response induced by these hormones in sensitive tissues.

How are Plasma Concentrations of Estradiol and Progesterone controlled?

The menstrual cycle involves the hypothalamus, anterior pituitary, and ovaries. Hormones from these tissues affect specific target organs. This cycle operates in postpubertal, premenopausal women.

Estradiol and progesterone are lipid-soluble steroid hormones. They can't be stored like protein hormones. When prompted, cells producing these hormones increase synthesis and release together. Their effects are gradual and sustained, necessitating changes in protein synthesis via cytoplasmic receptors altering gene expression.

How are Plasma Concentrations of Estradiol and Progesterone controlled?: Hypothalamus

Gonadotropin-releasing hormone (GnRH) is made by certain neurons in the brain's hypothalamus. It's released into the portal blood system connecting the hypothalamus base to the anterior pituitary gland. These neurons respond to estradiol and progesterone, primary estrogen and progestin, respectively.

How are Plasma Concentrations of Estradiol and Progesterone controlled?: Anterior Pituitary

Gonadotroph cells in the anterior pituitary release two hormones in response to GnRH: Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH supports ovarian follicle development and egg maturation, while LH triggers ovulation by releasing the egg from the follicle. In women, FSH and LH affect only the ovaries, while in men, they impact testicular function and testosterone synthesis.

How are Plasma Concentrations of Estradiol and Progesterone controlled?: Ovaries

Apart from producing eggs, the ovaries also release crucial hormones: estradiol (E) and progesterone (P). LH and FSH levels trigger their release. These hormones originate from different follicle cells and the corpus luteum (formed post-egg release). During pregnancy, the placenta takes over progesterone production.

Estrogens and Progestins wide use

as contraceptives \n -in maintenance of bone mass and function \n -to prevent occurrences cardiovascular pathologies \n -In cancer chemotherapy \n -in treatment of infertility

Hypothalamic Hormone

Gonadotrophin Releasing Hormone (GnRH)

Pituitary Hormones (anterior)

Follicle stimulating hormone (FSH) \n Luteinizing hormone (LH)

Ovarian Steroid Hormones

Estradiol (E) \n Progesterone (P)

Pharmacological Actions of Estrogen

Puberty leads to normal female maturation and reproductive ability. Mammary glands and uterine lining experience growth. Pituitary FSH and LH secretion decreases.

Outside reproduction, they impact heart attack, stroke risk, edema, bone health, affect estrogen-sensitive tumors, and influence brain neuron growth and function.

Mechanism of Action of Estrogen

\-activate cytosolic estrogen receptors  \n -alter gene expression \n -alter protein production

Estrogen receptor sites

Females: Uterus and mammary gland \n \n Females and Males: brain, pituitary gland, estrogen sensitive tumor cells, bone

Pharmacological Actions of Progestins

Endometrium of uterus \n -hyperplasia & vascularization (requires estrogen) \n -inhibition of uterine contractions (estrogen independent) \n decrease FSH & LH secretion from pitiuitary

Mechanism of Actions of Progestins

Activate cytosolic progesterone \n -alter gene expression \n -alter protein production

Progestin Receptor Sites

Females: Uterus \n Females and Males: Anterior pituitary gland

What are the effects of Estrogens?

Estrogens, whether natural or synthetic, share pharmacologic effects. Differences lie in administration, metabolism, potency, and use.

Physiological estrogen (estradiol) originates from ovaries (follicle, corpus luteum) and switches to placenta during pregnancy. Postmenopausal women get estradiol mainly from adrenal gland's testosterone conversion via aromatase.

Oral natural estrogens (estradiol, estriol, estrone) are poorly absorbed and swiftly eliminated, limiting therapeutic use. Conjugated, esterified, or synthetic estrogens are more stable orally, having longer action due to slower metabolism. They're also available as injections, implants, patches, or intrauterine devices for sustained release.

What are the effects of Progestins?

Progestins, whether natural or synthetic, share effects but vary in administration, metabolism, potency, and use.

Physiological progestin (progesterone) comes from ovaries (follicle, corpus luteum), shifting to placenta during pregnancy. Low levels exist in prepubertal and postmenopausal females.

Due to quick inactivation when taken orally, progesterone is injected intramuscularly. Synthetic progestins, more potent with prolonged effects, diverge from natural progesterone. They work orally and via injection, implant, or patch.

Daily Oral Contraceptive Pill: Overview

The first contraceptive pill had high-dose estrogen and was potent but linked to blood clot issues, heart attacks, and stroke deaths. Subsequent pills combine progestin and low-dose estrogen for efficacy and safety, while progestin-only options have concerns about reduced estrogen effects, possibly leading to osteoporosis.

Daily Oral Contraceptive Pill: History

The first contraceptive pill had risks due to high estrogen. Later, pills combined lower estrogen and progestins for safety. Introduced in the 1950s, it was marketed for other purposes, with contraception as a secondary effect. Pills have varied formulations, dosages, and schedules. Originally 21 days on, 7 off, women adjusted for convenience. Some newer pills extend on-drug periods similarly.

Daily Oral Contraceptive Pill: Monophasic vs. Multiphasic

Monophasic: Same dose of estrogen and progestin in every drug containing pill \n \n Multiphasic: Same dose of estrogen in every drug containing pill; progestin only in mid cycle

What formulations of estrogen and/or progestins are used in hormone replacement therapy (HRT)?

Hormone Replacement Therapy (HRT), mainly for postmenopausal women, prevents osteoporosis (estrogen), eases menopausal symptoms (hot flashes, estrogen), and reduces uterine cancer risk (progestin). Testosterone with estrogen can counter libido loss after menopause.

HRT comes as pills or patches with various formulations:

* Estradiol (PREMARIN)
* Estradiol and medroxyprogesterone (PREMPRO)
* Estradiol and norethindrone (COMBIPATCH)
* Estradiol and testosterone (ESTRATEST)

Clinical Use of  \n Estrogen and Progesterone Receptor Antagonists

There are several clinically used drugs which are antagonists or agonists at estrogen or progestin receptors. None of these drugs are steroids. None are used as contraceptives. \n -tamoxifen, raloxifene, clomiphene, and mifeoristone (RU486)

Hormones involved in control of plasma glucose concentration

Insulin, epinephrine, and glucocorticoids interact to maintain blood glucose balance. Insulin is key, regulating glucose, lipid, and protein metabolism, ensuring healthy levels between hyperglycemia and hypoglycemia.

Hormones involved in control of plasma glucose concentration: insulin

Produced in the pancreas' β cells, insulin is released into the blood. It prompts cells, including cardiac, skeletal muscle, adipose, and liver cells, to take up glucose, lowering blood sugar. It's known as a hypoglycemic agent.

Hormones involved in control of plasma glucose concentration: epinephrine

enhances insulin release - as part of the flight or fight reflex - to enhance glucose uptake from the blood by various cell types.

Hormones involved in control of plasma glucose concentration: glucocorticoids

hormones including cortisol secreted from the cortex of the adrenal gland causes release of glucose (derived from glycogen in the liver and muscle and from fat in adipocytes or fat cells)

What is Diabetes?

Characterized by excessive production of urine \n \n Diabetes Mellitus: sweet urine, presence of glycated hemoglobin Hb1Ac, lack of control of plasma glucose concentration \n \n Diabetes Insipidus: insipid urine, dysfunction of vasopressin synthesis or effect

Control of plasma glucose concentration

The body shifts between hyperglycemia and hypoglycemia. Insulin opposes effects of epinephrine and glucocorticoids.

Glucose levels:

* Hyperglycemia:

Signs of Hypoglycemia

\-palpitations \n -tachycardia \n -diaphoresis \n -anxiety \n -hunger \n -nausea

Signs of hyperglycemia

\-Hypotension \n -cardiac arrhythmias \n -stupor \n -sleepiness \n -ketoacidosis

Release of Insulin

cephalic component:

* Neurogenic: Triggered by CNS from sensory cues during eating.

Non-cephalic component:

* Pancreatic ß cells respond to GLP1 from stomach/intestine.
* GLP1 effect limited by DDP4.
* ß cells react to high glucose after carb intake.
* ß cells react to plasma epinephrine, boosting insulin release.

Non Diabetic ranges

blood glucose, urine glucose and urine volume are all in normal range  \n -glucose storage promoted -> glycogen and fat \n -blood FFA's and blood ketones in normal range

Diabetic ranges

type I and II: \n -blood glucose, urine glucose, and urine volume are all high \n \n Type I: \n -glucose storage reduced, and protein degraded \n -blood FFA's and blood ketones are high

Type I problems: short and long term

Short term: Hyperglycemia •Osmotic diuresis •Ketoacidosis  \n Long term: Regional (non productive) angiogenesis •(Distal Sensory) Neuropathy •Renal damage •Blindness •Tissue breakdown •Death of pancreatic β cells

Diabetes mellitus: insulin absent

Juvenile onset:

* Also IDDM, type I, insulin dependent.
* Lacks pancreatic insulin.
* Autoimmune disorder.
* Needs insulin, not controlled by diet or 'hypoglycemics'.
* May use anti-hyperglycemics alongside.
* Relies on injected insulin (rising insulin resistance risk).

Diabetes mellitus: insulin present

Adult onset:

* Also NIDDM, type II, non-insulin dependent.
* Issue with insulin secretion or resistance.
* Controlled by diet, hypoglycemics, anti-hyperglycemics.

What are the signs of hypoglycemia?

No medical conditions have hypoglycemia as a defining feature. Low blood glucose links to symptoms like palpitations, rapid heartbeat, anxiety, excessive sweating, hunger, nausea, and weakness.

What are the signs of hyperglycemia and what are the clinical problems of diabetes mellitus? Short term

Short-term hyperglycemia leads to:

* Stupor, convulsions, coma.
* Arrhythmias, ketoacidosis (abnormal fat metabolism).
* Glucosuria (high urine glucose).
* Osmotic diuresis (excess water excretion due to high urine glucose).

What are the signs of hyperglycemia and what are the clinical problems of diabetes mellitus? long term

In chronic uncontrolled diabetes (hyperglycemia):

* Glucosuria and dehydration cause thirst.
* Ketoacidosis (Type I) disrupts fat metabolism.
* Over time, issues include:
* Vascular problems, hypertension, heart conditions.
* Thickened capillaries, abnormal vessels.
* Kidney damage, neuropathy, sensory loss, retinal issues, blindness.
* Tissue damage can lead to amputation.
* Type II diabetes may lose pancreatic β cells, resembling Type I.

type II

ype II diabetes:

* Associated with hypertension, obesity, and high LDL.
* Traditionally adult-onset, now rising in obese children.
* Insulin-sensitive: Pancreas function impaired, low insulin.
* Insulin-induced pharmacologically to reduce blood glucose.
* Insulin-resistant: Pancreas fine, high insulin but reduced sensitivity.
* Increased insulin sensitivity with drugs useful, but not insulin inducers.
* Hyperinsulinemia damages pancreas β cells, worsening hyperglycemia.
* Drugs affect glucose renal excretion, hepatic handling, helping both sensitivities.
* Could be one spectrum, not classified as subtypes.
* Behavior changes and drugs manage Type II diabetes.

type I

Type I diabetes:

* Autoimmune disease destroys pancreatic β cells, preventing insulin production.
* Not triggered by plasma glucose rise, so insulin can't regulate.
* Also known as juvenile-onset diabetes.
* Needs insulin injections, not behavior changes.
* Insulin secretion inducers ineffective.
* Some Type I diabetics show insulin resistance, akin to Type II.
* Need insulin, even when combined with insulin resistance.

Type I and II

In both diabetes types, high blood sugar causes hemoglobin glycosylation, forming HbA1c. HbA1c's long half-life (90+ days) indicates glucose control over 3 months. Elevated HbA1c triggers cardiovascular changes in poorly controlled diabetics.

Hypoglycemic Drugs

Diabetes treatment depends on type:

* Type I: Insulin.
* "Insulin-sensitive Type II": Insulin-like drugs (tolbutamide, glyburide, glipizide) or insulin release stimulants (repaglinide).
* "Insulin-resistant Type II": Independent hypoglycemics (metformin, "-flozin" drugs). Other options include exenatide, dulaglutide, sitagliptin, alogliptin, canagliflozin, dapagliflozin.

Antihyperglycemic Drugs

iabetes treatment varies by type:

* Type I: Insulin, plus metformin and "-flozin" drugs, and antihyperglycemic drugs.
* Type II:
* First strategy: Hypoglycemic drugs, regardless of action.
* Second strategy: Anti-hyperglycemic drugs, like "glitazone" drugs.
* "Glitazones" enhance insulin effectiveness, stimulate glucose uptake by muscle and heart, and hepatic glucose storage.
* Examples: pioglitazone, rosiglitazone.

Thyroid Hormones

\-T3 and T4 \n -each has two link tyrosine amino acids and each tyrosine may be iodinated at one or two positions \n -more T4 than T3 synthesized, secreted and present in blood \n -T4 converted to T3 in blood \n -T3 is the active component

Importance of Iodine

critical to hormone production  \n -too little causes thyroid enlargement and low level of T3 and T4 in the blood \n -too much causes thyroid enlargement and low level of T3 and T4 in the blood

Hypothyroidism

Non-toxic Goiter:

* Low iodine > big thyroid > low T3, high TSH. Chronic Thyroiditis (Hashimoto's):
* Autoimmune > low TSH receptors > low T3, high TSH. Surgical/Chemical Thyroid Removal:
* Low T3 > high TSH. Idiopathic:
* Cause unknown.

Hyperthyroidism

raves Disease:

* Autoimmune.
* Antibody activates TSH receptor.
* High T3 > low TSH. TSH-Secreting Pituitary Tumor:
* Thyroid function normal.
* High T3 > high TSH. Idiopathic:
* Cause unknown.

Thyroid gland: Function & dysfunction

Thyroid gland and T3 hormone vital for normal function. Dysfunction: hypothyroidism (low T3) or hyperthyroidism (high T3). Both widespread, treatable effectively.

Electric Activity in the Heart

View the heart as an electrical circuit linked to a mechanical pump. Both aspects need to work well individually and in harmony for proper contraction.

Normal Electrical Conduction Pathway in the Heart

S-A Node - Atria - A-V Node - His-Purkinje System - Ventricles. Seen in single cell action potentials and ECG. P wave: Atrial depolarization. QRS complex: Ventricular depolarization. T wave: Ventricular repolarization.

ECG

ECG records heart's electrical activity using skin electrodes. ECG components depend on:

* Size of underlying cell event.
* Number of synchronous cells.
* Structural alignment for electrode detection. Large ECG event = large, synchronous cell event detected. Small ECG event = small, asynchronous cell event detected.

Excitability

Ability of a cell to initiate an action potential when stimulated and, when appropriate, to contract in response to the depolarization associated with the action potential

Automaticity

Action potential can arise without or outside normal timing stimulus. S-A Node cells drive heart's electrical cycle; others follow. Damaged or hypoxic cells might show automaticity, becoming drivers instead of followers. Abnormal automaticity site: ectopic site of automaticity, or ectopic automaticity.

Conduction Velocity

Speed at which wave of electrical excitation spreads; a term particularly applicable to the A-V Node

Refractory Period

Period of time after an action potential for which a cell remains unexcitable - unable to generate an action potential - and unable to contract.

Factors Influencing Cardiac Performance

\-Afterload \n -Contractility \n -Conductivity \n -Heart Rate \n -Stroke Volume \n -Cardiac Output \n -Preload

Afterload

Impedance (resistance) against which heart must pump

Contractility

Vigorousness with which heart muscle contracts

Conductivity

Ability of tissue to conduct action potential

Heart Rate

Frequency of cardiac wave of excitation and contraction occurs

Stroke Volume

Volume of blood pumped by heart in a single heart beat

Cardiac Output

Product of stroke volume and heart rate; volume of blood pumped by hear per minute

Preload

Diastolic loading (filling with blood) of atria and ventricles

What is the Disturbance of Automaticity?

Alteration of normal activity at S-A node: sinus bradycardia and sinus tachycardia  \n \n Induction of automaticity in tissue not normally exhibiting such activity

What is the Disturbance of Automaticity? Alteration of normal activity at S-A node: sinus bradycardia and sinus tachycardia

hese scenarios can happen spontaneously or due to drugs. Some drugs affect heart rate: β1 agonists and muscarinic antagonists increase heart rate; β1 antagonists and muscarinic agonists decrease it. Generally fine if atrial-ventricular coordination is maintained and fainting from low blood pressure doesn't result due to excessive bradycardia or cardiac arrest.

What is the Disturbance of Automaticity? Induction of automaticity in tissue not normally exhibiting such activity

Heart damage can cause automaticity, making a damaged part a "driver" of heart's activity. Can happen in atria or ventricles, causing atrial-ventricular discoordination and inefficiency. Risk of cardiac arrest, heart attack, and clot formation. Ectopic focus is the origin of abnormal activity. May also lead to clot formation, causing heart attack or stroke.

What is the disturbance of conduction?

AV node slowdown leads to ventricular delay, inefficiency, and risk of arrest.

Reentry: Disrupted pathway can create new routes. Abnormal circuits cause repeated reentry. Atrial fibrillation from rapid atrial reentry. Ventricular fibrillation from uncontrollable ventricular reentry. Atrial less severe, ventricular more dangerous, causing cardiac failure.

What are the prime features of arrhythmias?

Automaticity and Conduction Issues:

Arrhythmias: Coordination loss between atria and ventricles.

Conduction Disturbances (A-V Node):

* 1st degree block: delayed conduction, coordination.
* 2nd degree block: occasional atrial-ventricular miscoordination.
* 3rd degree block: complete block, no coordination.

Pharmacological treatment not covered in this course.

Antiarrhythmics

Anti-arrhythmic drugs restore normal cardiac electrical activity and contractile function. Excessive use can cause arrhythmias in those with arrhythmias or normal rhythm.

Types of Angina

Classical or Stable  \n \n Unstable \n \n Variant or Vasospastic

Classical or Stable Angina

Thrombus or plaque blocks coronary vessels. No issues at rest. During exercise, insufficient blood flow causes heart hypoxia.

Unstable Angina

Thrombus or plaque blocks coronary vessels. Even at rest, insufficient blood flow leads to heart hypoxia. Predictive of heart attack due to prolonged ischemia.

Variant or Vasospastic Angina

Spontaneous coronary constriction without thrombus or plaque. Pharmacologically treatable due to absent obstruction and vessel responsiveness.

Risk Factors for Angina

Chronic: Diabetes, age, anxiety, obesity \n \n Acute: stress, physical exertion, rapid temperature change

What is the prime objective in treatment of angina?

Main goal: Restore heart's oxygen balance by increasing coronary blood flow or reducing heart's work. Decrease work by lowering cardiac output via heart rate or peripheral resistance.

Drugs Available for Angina

Nitrates, ß-adrenergic Receptor Blockers, Calcium Channel Blockers

Symptoms and Causes of Chronic Heart Failure (CHF)

Symptoms:

* Elevated blood volume and pressure
* Edema
* Capillary congestion with slow erythrocyte movement
* Dyspnea (shortness of breath)
* Fatigue

Associated with:

* Coronary artery disease
* Rheumatic heart disease
* Hypertension
* Arrhythmias
* Cardiac valve dysfunction
* Pulmonary disease

Pathophysiological features of CHF

Healthy response to insufficient blood flow:

* Myocardial hypertrophy for increased contractility and pumping
* Increased sympathetic activity: venous constriction, increased contractility, vasoconstriction, increased heart rate
* Hormonal changes, including renin-angiotensin system activation

In CHF:

* Response compromised due to reduced heart muscle mass
* Increased cardiac work risky, can lead to hypoxia, angina, heart attack, death

Objectives in treatment of Chronic Heart Failure?

Increase blood flow to all tissues

Objectives in pharmacological treatment of Chronic Heart Failure?

Enhance cardiac output without causing hypoxia:

* Increase contractility
* Decrease blood volume and pressure

Reduce cardiac workload:

* Decrease blood volume and pressure

What is the relationship between cardiac output and heart filling

In normal individuals:

* Increased blood return to the heart increases cardiac output (up to a limit).
* Cardiac Output = Stroke Volume
* Within a certain range of Cardiac Output, fatigue is felt.
* Within a certain range of Ventricular End Diastolic Pressure, shortness of breath (dyspnea) occurs.

How can the Heart be Targeted Therapeutically in Chronic Heart Failure?

Various methods can increase cardiac output by making the heart work harder. However, this approach can be risky for CHF patients, as their weakened hearts may lead to arrhythmias and heart attack due to the increased workload.

How can the Kidney be targeted therapeutically in congestive heart failure?

Use of diuretics with primary action in kidney and with primary action outside of kidney

What are the Physiological Functions of the Kidney? Filtration

Ultrafiltration of the plasma occurs in each glomerulus of the kidney: ultrafiltrate contains water, ions (Na, K, Cl etc), glucose, and very small amounts of amino acids and proteins.

Aspects of Renal Physiology

he kidneys consist of nephrons, each comprising a glomerulus and a tubule. Filtration at the glomerulus removes water, electrolytes, glucose, and drugs from plasma. The tubule reabsorbs water, ions, glucose, and drugs. The kidneys produce about 125ml/min of ultrafiltrate, from which about 1ml/min of urine is formed.

What are the Physiological Functions of the Kidney? Reabsorption

Nephron reabsorption involves passive and active processes. Glucose and non-ionized compounds are passively reabsorbed. Ions are reabsorbed actively and passively in different tubule segments: Proximal tubules (HCO3, Na, Cl, H2O), Descending Loop (H2O), Ascending Loop (Na, Cl, Mg, Ca, K), Distal tubule (Na, K, Cl), Collecting duct (Na via transporters, Na and Cl passively, H2O under ADH control).

What are the Physiological Functions of the Kidney? Acid-base Control.

H and HCO3 excretion in urine regulate plasma pH.

* Metabolic Acidosis: Decreased pH due to excessive acid production or HCO3 excretion. Treated with oral/IV HCO3.
* Metabolic Alkalosis: Increased pH from excess gastric acid or HCO3 intake. Treated with NaCl+KCl to increase HCO3 excretion.
* Respiratory Acidosis: Decreased pH from hypoventilation and CO2 retention. Treat respiratory issue, use oral/IV HCO3.
* Respiratory Alkalosis: Increased pH from hyperventilation and CO2 loss. Treat with CO2 inhalation or rebreathing expired air.

What Types of Diuretic Drug are Available?

Diuretic drugs increase urine volume. Some work directly in the kidneys, while others act elsewhere but have secondary effects in the kidneys. Diuretics enhance the elimination of all drugs excreted in urine, which can be helpful in overdose situations but problematic for therapeutic drugs. Kidney-focused diuretics can be "K wasters" or "K sparers," both increasing Na and water excretion.

"K wasting" diuretics

Diuretics reduce sodium and water reabsorption, primarily in the distal tubule and loop of Henle. This increases sodium levels in the collecting duct, prompting excess sodium reabsorption through the Na/K exchanger. Despite increased sodium reabsorption, excess potassium is excreted, causing hypokalemia.

"K sparing" diuretics

Collecting duct diuretics decrease sodium and water reabsorption while sparing potassium. This is due to reduced activity of the Na/K exchanger mechanism, leading to hyperkalemia. Aldosterone secretion and angiotensin II levels regulate this process. These diuretics affect the number or function of exchangers, increasing water excretion.

Why are Diuretics Used?

Diuretics decrease blood volume, reducing blood pressure and cardiac workload in conditions like hypertension and heart failure. They also enhance drug excretion in overdose situations.

How Much Does Urine Volume Increase with Diuretic Drugs?

Diuretics can increase urine volume significantly, even up to 3-10 ml/min, causing frequent restroom visits. Higher urine output leads to dehydration and triggers thirst. Decreased blood volume prompts the body to counteract with vasoconstriction, increased cardiac output, and water retention.

K Wasters

Loop of Henle and distal tubule diuretics increase urine volume and K excretion, reducing plasma K levels ("K wasting diuretics"). They can be used with "K sparing diuretics" for maximum effect. Examples include thiazides (hydrochlorothiazide, trichlormethiazide) and high ceiling/loop diuretics (furosemide, ethacrynic acid).

K Sparings

Collecting duct diuretics increase urine volume while reducing K excretion ("K sparing diuretics"). They can be used alongside "K wasting diuretics" to enhance diuretic effect with minimal K impact. Examples: mineralocorticoid receptor antagonists (spironolactone, eplerenone), and Na pore blockers (triamterene, amiloride).

CA Inhibitors

carbonic anhydrase (CA) converts carbonic acid to H+ and HCO3-. Inhibition of CA by drugs like acetazolamide reduces Na and HCO3 reabsorption, decreases H2O reabsorption, and reduces H excretion. This leads to increased urine pH and more basic urine, while making plasma more acidic.

Non Renal Action Drugs

Not all drugs that cause diuresis have a direct action in the kidney. Osmotic diuretics and Angiotensin converting enzyme inhibitors cause diuresis through primary actions outside of the kidney. \n \n osmotic diuretics: mannitol \n \n Inhibitors of angiotensin converting enzyme: captopril, enalapril, quinapril

Osmotic Diuretics

Most osmotic diuretics have become less popular due to irritation after intravenous infusion. Mannitol is the primary one still in use, effective and non-irritating. Its use is infrequent, requiring close clinical observation and specific occasions.

Inhibitors of Angiotensin Converting Enzyme

Angiotensin II (AngII) is a peptide hormone formed from Angiotensin I by angiotensin converting enzyme (ACE) and renin. AngII has two key blood pressure effects: increasing aldosterone release and vasoconstriction. ACE inhibitors reduce AngII, leading to vasodilation, reduced aldosterone, increased urine volume, and lowered blood pressure.

Blood Pressure Control

Blood pressure = Cardiac output x Total peripheral resistance Cardiac output = Heart rate x Stroke volume Total peripheral resistance depends on vascular diameter, blood viscosity, and vascular length. Sympathetic nervous system and renin angiotensin system control vascular diameter. Blood viscosity changes with water balance, and vascular length remains stable after growth.