CASE 8:

A 15 year old schoolgirl was admitted to hospital as an emergency while on holiday, Her parents believed
her to be allergic to nuts. The emergency admission occurred following a single lick of a vanilla-peanut
butter ice cream. Within seconds, she developed angioedema of her lips and tongue, difficulty of breathing
and felt lightheaded. Following an emergency call, she was injected with intramuscular epinephrine and
intravenous hydrocortisone by the paramedical service and was admitted to the hospital overnight. She
made a rapid and uneventful recovery
1. Molecular pharmacology underlying the actions of Sympathomimetic Drugs: refer table below
2. End-organ system effect:
3. Classification of different sympathomimetic drugs

Epinephrine A1=A2; B1=B2 Anaphylactic shock

Norepinephrine A1=a2; B1>B2 Increase peripheral resistance and SBP and DBP
Dopamine D1=D2 >> B >> a
Drugs Receptor Therapeutic Uses
DIRECT-ACTING SYMPATHOMIMETICS
Midodrine 1 selective agonist orthostatic hypotension, typically due to impaired
autonomic nervous system function
Phenylephrine pure  agonist mydriatic agent frequently used to facilitate examination of the retina
decongestant for minor allergic hyperemia and itching of the
conjunctival membranes.
Clonidine Alpha2-selective agonists treatment of hypertension
Methyldopa - decrease blood pressure
Guanabenz through actions in the
Guanfacine CNS that reduce
moxonidine, rilmenidine sympathetic tone Hypertension = fewer CNS side effects
 dexmedetomidine (“sympatholytics”) even Prominent sedative effects and used in anesthesia
tizanidine though direct application Muscle relaxant
Apraclonidine and brimonidine to a blood vessel may Topical: glaucoma to reduce IOP
cause vasoconstriction.
Oxymetazoline α agonist Topical decongestant = promote constriction of the
vessels in the nasal mucosa and conjunctiva
Isoproterenol (isoprenaline) β-receptor agonist (nonselective) Potent vasodilator
Dobutamine Selective β-1 agonist Cardiogenic shock, acute heart failure
Albuterol Selective β-2 agonist Asthma
MIXED-ACTING SYMPATHOMIMETICS
Ephedrine Used earlier in asthma, mild CNS stimulant
Pseudoephedrine available over the counter as a component of many decongestant
mixtures
INDIRECT-ACTING SYMPATHOMIMETICS
Amphetamine use and misuse as a CNS stimulant
Methamphetamine (N higher ratio of central to peripheral actions.
methylamphetamine)
Methylphenidate may be effective in children with attention deficit hyperactivity disorder
Modafinil Psychostimulant
improve wakefulness in narcolepsy
Tyramine marked increases in blood pressure
MOA of Indirect-acting drugs:
▪ enter the sympathetic nerve ending and displace stored catecholamine transmitter. Such drugs have been called amphetamine-like or
“displacers.”
▪ Second, they may inhibit the reuptake of released transmitter by interfering with the action of the norepinephrine transporter, NET.

4. Type of antagonism produced by epinephrine on Histamine

- Functional anatagonism = act on different receptors producing opposite effects
- Histamine receptor causes the blood vessels to expand or vasodilate, causes a dangerous drop in BP, and Bronchoconstriction.
- Epinephrine antagonizes Histamine effects by activating adrenergic receptors alpha and beta receptors w/c results to vasoconstriction and
bronchodilation respectively
5. MOA of Epinpherine in relieving allergic reactions
- Epinephrine is an alpha 1&2 and Beta 1&2 agonist w/c is a very potent vasoconstrictor and stimulant
- rise in SBP = positive inotropic and chronotropic actions on the heart (b1)
- vasoconstriction induced in many vascular beds (a receptrors)

CASE 9:
A 12 year old girl present to your office with a sore throat and fever. You diagnose her with pharnyngitis
caused by group A Beta- Hemolytic streptococcus. She is given an IM injection of penicillin. Approximately 5
minutes later, she if found to be in respiratory distress and audible wheezing. Her skin is mottled and cool,
she is tachycardic (rapid heart rate) and her blood pressure has fallen to 70/20 mmHg. You immediately
diagnose her as having an anaphylactic reaction to the penicillin and give an SC injection of epinephrine.

1. Pathophysiology of anaphylactic reaction due to a drug

2. Responses of the activation of the different epinephrine receptors
- Epinephrine: affinity: α1 = α2; β1 = β2

ALPHA ADRENOCEPTORS
G Protein Cellular response Organ Effects
 IP3 and DAG
1 Gq – phospholipase C
 calcium influx
Arterial and venous constriction positive inotropy
reflex bradycardia
Tyrosine kinase stimulation
Splanchnic, skin, nasal mucosa vasoconstriction
vasoconstriction
 Eye: Iris Muscle Mydriasis

Ductus deferens, seminal Normal ejaculation

vesicles, prostate
1A
Urethral sphincter, Prostate Contraction, urinary continence = urinary
retention
Gi – adenylyl cyclase  cAMP Peripheral Vessels Vasodilation
Platelet aggregation - Local, rapid IV, higher doses =
2 vasoconstriction
- Systemic low doses =  BP, inhibit
sympathetic tone

EYE Increase outflow of aqueous humor

Mouth Xerostomia

Fat cells Inhibit lipolysis

Pancreatic islets Decrease insulin secretion

Renin Inhibits renin secretion

BETA ADRENOCEPTORS
G Protein Cellular response Organ Effects
1 Gs - adenylyl cyclase  cAMP SA Node Positive chronotropy, increase pacemaker
 Ca2+ influx in cardiac cells activity

AV node Positive dromotropy

Decrease refractory period

Intrinsic Myocardial contractility Positive inotropy

Accelerates relaxation

Fat cells Increased lipolysis, enhanced release of Free FA

and glycerol in blood

Renin Increased renin secretion

2 Gs - adenylyl cyclase  cAMP Bronchial smooth muscles Bronchodilation
Gq  K+ influx =  EC K+
 Pancreatic islets Increase insulin secretion

Muscle and Liver Increased glycogenolysis

3. Adrenoceptor primarily mediates the vascular response? Discuss the effect of epinephrine on this
patient’s vascular system?
- Alpha1 receptors are widely expressed in vascular beds, and their activation leads to arterial and
venous vasoconstriction. Their direct effect on cardiac function is of relatively less importance. A
relatively pure α agonist such as phenylephrine increases peripheral arterial resistance and decreases
venous capacitance. The enhanced arterial resistance usually leads to a dose-dependent rise in blood
pressure (Figure 9–6). In the presence of normal cardiovascular reflexes, the rise in blood pressure
elicits a baroreceptor-mediated increase in vagal tone with slowing of the heart rate, which may be
quite marked.
- Positive inotropy; reflex bradycardia
- EPINEPHRINE ON VASCULAR SYSTEM:
o Epinephrine (adrenaline) is an agonist at both α and β receptors. It is therefore a very potent
vasoconstrictor and cardiac stimulant.
o Positive inotropic and chronotropic actions on the heart (predominantly β1 receptors)
▪ rise in systolic blood pressure
o vasoconstriction induced in many vascular beds (α receptors)
▪ rise in systolic blood pressure
o Beta-2 receptors activation = vasodilation in some vascular beds
▪ Decrease total peripheral resistance, explaining the fall in diastolic pressure that is sometimes seen with epinephrine injection
▪ Net effect = maintain or slightly increase systolic pressure and to lower diastolic pressure → mean blood pressure is decreased
4. Adrenoceptor primarily mediates the respiratory system response? Discuss the effect of epinephrine on this patient’s respiratory system
- Epinephrine also activates β2 receptors in some vessels (eg, skeletal muscle blood vessels), leading to their dilation
- Beta-2 receptors primarily mediates the bronchial smooth muscle = bronchodilation
- Anaphylactic shock → bronchoconstriction → respiratory distress and audible wheezing in patient = administer epinephrine → B2 activation →
bronchodilation
5. Compare Phenylephrine, Epinephrine, and Isoproterenol as to their cardiovascular response

6. Why Epinephrine is the drug of choice to relieve anaphylactic shock, and what is the dose.
- Anaphylactic shock and related immediate (type I) IgE-mediated reactions affect both the respiratory and the cardiovascular systems.
- The syndrome of bronchospasm, mucous membrane congestion, angioedema, and severe hypotension usually responds rapidly to the parenteral
administration of epinephrine, 0.3–0.5 mg (0.3–0.5 mL of a 1:1000 epinephrine solution).
- Epinephrine activates α, β1, and β2 receptors, all of which may be important in reversing the pathophysiologic processes underlying anaphylaxis.
- Intramuscular injection may be the preferred route of administration, since skin blood flow (and hence systemic drug absorption from subcutaneous
- injection) is unpredictable in hypotensive patients. In some patients with impaired cardiovascular function, intravenous injection of epinephrine may
be required.
- It is recommended that patients at risk for anaphylaxis carry epinephrine in an autoinjector (EpiPen, Auvi-Q) for self-administration
Case 10:
A 65 year old woman is admitted to the intensive care unit (ICU) of the hospital with sepsis caused by
urinary tract infection. She is hypotensive, with blood pressure of 80/40mmhg and has elevated heart rate
(tachycardia) and decreased urine output (oliguria), Along with the institution of appropriate antibiotic
therapy and IV fluids, a decision is made to start her on an IV infusion of dopamine to attempt to raise her
blood pressure
1. Effects of sympathomimetic agents on peripheral organ systems
- Activation of β2 receptors in bronchial smooth muscle leads to bronchodilation, and β2 agonists are important in the treatment of asthma
- In the eye, the radial pupillary dilator muscle of the iris contains α receptors; activation by drugs such as phenylephrine causes mydriasis (see Figure
6–9). Alpha2 agonists increase the outflow of aqueous humor from the eye and can be used clinically to reduce intraocular pressure. In contrast, β
agonists have little effect, but β antagonists decrease the production of aqueous humor and are used in the treatment of glaucoma (see Chapter 10).
- In genitourinary organs, the bladder base, urethral sphincter, and prostate contain α1A receptors that mediate contraction and therefore promote
urinary continence. This effect explains why urinary retention is a potential adverse effect of administration of the α1 agonist midodrine, and why
α1A antagonists are used in the management of symptoms of urinary flow obstruction.
- Alpha-receptor activation in the ductus deferens, seminal vesicles, and prostate plays a role in normal ejaculation and in the detumescence of
erectile tissue that normally follows ejaculation.
- The salivary glands contain adrenoceptors that regulate the secretion of amylase and water. However, centrally acting sympathomimetic drugs, eg,
clonidine, produce symptoms of dry mouth. It is likely that CNS effects are responsible for this side effect, although peripheral effects may
contribute.
- The apocrine sweat glands, located on the palms of the hands and a few other areas, are nonthermoregulatory glands that respond to psychological
stress and adrenoceptor stimulation with increased sweat production. (The diffusely distributed thermoregulatory eccrine sweat glands are
regulated by sympathetic cholinergic postganglionic nerves that activate muscarinic cholinergic receptors; see Chapter 6.)
2. Classify major sympathomimetic agents and give their receptors specifity and therapeutic uses.
- Refer to case 8 no. 3

3. Describe the adverse effects

4. Effects of low-dose dopamine
 5. Which receptors mediate these effects refer to pictures above
6. Effects of higher dose dopamine and which receptors mediate these refer to pictures above

Case 11:
52 year-old woman was admitted to hospital with recurrent episodes of: chest and abdominal pain,
dyspnea, palpitations, diaphoresis, Continuos blood pressure recordings revealed: rhythmic alteration
between episodes of severe hypertension and episodes of hypotension. This cyclic hemodynamic crisis
continued for 2 hours, with each cycle lasting around 15 minutes.
1. Diagnosis and Basis:
- Pheochromocytoma
o Pheochromocytoma is a tumor of the adrenal medulla or sympathetic ganglion cells. The tumor secretes catecholamines, especially
norepinephrine and epinephrine
- Palpitations + diaphoresis + abdominal pain
- Rhythmic alteration between episodes of severe htn and episodes of hypoTN for 2hrs w/ each round lasting 15mins
- High levels of metanephrine, epinephrine
2. Pathophysiology
3. Drugs used to treat this condition and MOA
- Alpha-receptor antagonists are most useful in the preoperative management of patients with pheochromocytoma (Figure 10–4). Administration of
phenoxybenzamine in the preoperative period helps to control hypertension and tends to reverse chronic changes resulting from excessive
catecholamine secretion such as plasma volume contraction, if present.
o Phentolamine
 ▪
potent competitive antagonist at both α1 and α2 receptors (Table 10–1). Phentolamine reduces peripheral resistance through
blockade of α1 receptors and possibly α2 receptors on vascular smooth muscle.
o Phenoxybenzamine
▪ binds covalently to α receptors, causing irreversible blockade of long duration (14–48 hours or longer). It is somewhat selective for
α1 receptors
• attenuation of catecholamine-induced vasoconstriction
▪ The drug also inhibits reuptake of released norepinephrine by presynaptic adrenergic nerve terminals.
▪ Phenoxybenzamine blocks histamine (H1), acetylcholine, and serotonin receptors as well as α receptors (see Chapter 16).
- Beta-receptor antagonists may be required after α-receptor blockade has been instituted to reverse the cardiac effects of excessive catecholamines.
- sometimes treated with metyrosine (α-methyltyrosine), the α-methyl analog of tyrosine. This agent is a competitive inhibitor of tyrosine
hydroxylase, the rate-limiting step in the synthesis of dopamine, norepinephrine, and epinephrine (see Figure 6–5). Metyrosine is especially useful in
symptomatic patients with inoperable or metastatic pheochromocytoma.
o Because it has access to the CNS, metyrosine can cause extrapyramidal effects due to reduced dopamine levels.
4. Alpha adrenoceptor antagonist
5. Other therapeutic indications and adverse effects of alpha adrenoceptor antagonist

Alpha adrenoceptors antagonsits Drugs Therapeutic indications Adverse effects

Alpha-1 selective antagonist Phenoxybenzamine pheochromocytoma Orthostatic hypotenstion
Tachycardia
Nasal stuffiness
Inhibition of ejaculation
Fatigue, sedation, nausea
Alpha-2 and alpha 1 Phentolamine Pheochromocytoma Severe tachycardia
Reverse local anesthesia in soft Arrhythmias
tissue sites Myocardial ischemia
Alpha 1 >> alpha 2 Prazosin Hypertension mgt
Alpha-1 selective antagonist Terazosin Hypertension
Urinary retention symptoms due to
BPH
Doxazosin Tx of hypertension and BPH
Competitive alpha-1 antagonist Tamsulosin BPH = mediate prostate smooth Orthostatic hypotension
Alpha 1a and 1d >> alpha 1b muscle contraction increased risk of the intraoperative
floppy iris syndrome (IFIS) after
cataract surgery
Alpha1 selective blocker Alfuzosin BPH Inc. risk of QT prolongation
Alpha 1a Silodosin BPH
Alpha 1 selective Indoramin antihypertensive
Alpha 1 >> alpha 2 and 5HT1a agonist Urapidil Anti HTN
 Alpha 1 and beta 1 Labetalol, carvedilol
Alpha antagonist but a potent chlorpromazine Hypotension
dopamine antagonist and haloperidol
Alpha 1 blocker Trazodone
reversible α-receptor blockade ergotamine
and dihydroergotamine,
Alpha 2 selective Yohimbine Orthostatic hypotension hypertension
Male erectile dysfunction

Case 12:
A 45-year-old man was referred to your clinic by a barangay health worker. He was noted to have persistently elevated
blood pressure readings and was given metoprolol. He is not a smoker and is not diabetic. He had asthma as a child, but has
no had any recent wheezing episodes. He told you that the health center has run out of metoprolol but has plenty of
propranolol and ask if he can use propranolol instead of metoprolol.
1. Beta blockers classification and MOA
- All of the clinically available B-Blockers are competitive antagonists
- Non-selective B-blockers act at both B1 and B2 receptors
o Nadolol and timolol = more potent than propranolol
o Carteolol
o Nadolol = long DOA
o Timolol = reduces production of aqueous humor in the eye
▪ Topical: tx of open-angle glaucoma
▪ Systemic tx of hypertension
o Propranolol
- Selective are cardio selective and primarily block B1 receptors
o Acebutolol
o Atenolol
o Bisoprolol
o Betaxolol
o Esmolol
o Metoprolol
o Nebivolol
- Antagonist with partial agonist activity = weakly stimulate both b receptors and have intrinsic sympathomimetic activity
o Stimulate b receptor yet inhibit stimulation by more potent endogenous catecholamines
▪ Diminish effect on cardiac rate and cardiac output compared to Bblockers without ISA
o Minimize the disturbances of lipid and carbohydrate metabolism = do not decrease plasma HDL levels
o Acebutolol
 o Pindolol
- Antagonist of both alpha and beta receptors
o Peripheral vasodilation = dec. BP
o Carvedilol – decrease lipid peroxidation and vascular wall thickening = for heart failure
o Labetalol
2. Properties
- Pure antagonist
o The occupancy of a β receptor by such a drug causes no activation of the receptor.
- Partial agonist
o they cause partial activation of the receptor, albeit less than that caused by the full agonists epinephrine and isoproterenol
o inhibit the activation of β receptors in the presence of high catecholamine concentrations but moderately activate the receptors in the
absence of endogenous agonists
o evidence suggests that some β blockers (eg, betaxolol, metoprolol) are inverse agonists—drugs that reduce constitutive activity of β
receptors—in some tissues. The clinical significance of this property is not known.
- A. Absorption
o Most of the drugs in this class are well absorbed after oral administration; peak concentrations occur 1–3 hours after ingestion. Sustained
release preparations of propranolol and metoprolol are available.
- C. Distribution and Clearance
o The β antagonists are rapidly distributed and have large volumes of distribution.
o Most β antagonists have half-lives in the range of 3–10 hours. A major exception is esmolol, which is rapidly hydrolyzed and has a half-life of
approximately 10 minutes.
3. Different cardio selective Beta blockers and clinical uses
- Beta-blocking drugs given chronically lower blood pressure in patients with hypertension
- probably include suppression of renin release and effects in the CNS
- Beta-receptor antagonists have prominent effects on the heart (Figure 10–6) and are very valuable in the treatment of angina (see Chapter 12) and
chronic heart failure (see Chapter 13) and following myocardial infarction (see Chapter 14).
- The negative inotropic and chronotropic effects reflect the role of adrenoceptors in regulating these functions.
- Slowed atrioventricular conduction with an increased PR interval is a related result of adrenoceptor blockade in the atrioventricular node.
- In the vascular system, β-receptor blockade opposes β2-mediated vasodilation. This may acutely lead to a rise in peripheral resistance from
unopposed α-receptor–mediated effects as the sympathetic nervous system discharges in response to lowered blood pressure due to the fall in
cardiac output.
- Metoprolol
o Myocardial infarction
o Angina pectoris
o Tachycardia
o Heart failure
- Esmolol
o acute perioperative arrhythmias
o prevent treat tachycardia
o tx of SVT
 - Atenolol
o Hypertension
o CHP
o Arrhythmias
o Angina pectoris
- Acebutolol
o HTN
o Ventricular and atrial cardiac arrhythmias
o Acute MI
- Betaxolol
o HTN
o Angina pectoris
o glaucoma
- Nebivolol
o most highly selective β1-adrenergic receptor blocker
o HTN
4. Effect of metoprolol in CV system
- B1 selective antagonists lowers BP along w/ renin release inhibition
5. Why use beta antagonists with caution in asthmatics?
- Beta antagonist can cause bronchoconstriction which will exacerbate bronchospasms in asthmatic patients
6. Should you change the px drug to propranolol? Explain
- No. Propranolol is nonselective and can block B2 receptor causing bronchoconstriction = can precipitate exacerbation in patients with asthma
- CI in px with asthma
7. AE of non-cardio and cardio selective beta blockers
- Non-cardio
o Propranolol
▪ Bronchoconstriction
▪ CNS: Depression, dizziness, lethargy, fatigue, weakness, visual disturbances, hallucinations, short term memory loss, emotional
lability, vivid dreams
▪ Exacerbation of COPD or asthma
o Cold hands
o Hyperglycemia
o Bradycardia
- Cardio:
o Bradycardia
o Hypotension
o AV nodal block
o caution is required in patients with severe peripheral vascular disease or vasospastic disorders
Case 13
A 64-year-old woman with a history of two previous myocardial infarctions (MIs) comes to the emergency room with
shortness of breath. In the previous 2 weeks, she has developed dyspnea with exertion and swelling of her legs. She sleeps
on three pillows because she coughs and gets short of breath if she tries to lie flat. In the emergency department, she is
sitting upright, appears to be in moderate respiratory distress, and is tachycardic and hypertensive. She has jugular venous
distention to the angle of her jaw. On auscultation of her lungs, wet rales are heard bilaterally. She has pitting edema of
both lower lesgs up to her knees. A chest X-ray confirms the diagnosis of pulmonary edema. She is placed on oxygen
therapy and immediately given an IV injection of furosemide.
1. MOA of diuretics agents and site of action:
- Carbonic anhydrase inhibitors
o Carbonic anhydrase enzyme
▪ Present in many nephron sites but predominant in PCT
▪ Catalyzes dehydration of H2CO3 to CO2 at the luminal membrane and rehydration of CO2 to H2CO3 in the
cytoplasm
o Blocks carbonic anhydrase = blunt NaHCO3 reabsorption and cause diuresis
o Acetazolamide
- SGLT 2 Inhibitors
o Normally, PCT reabsorbs almost all of the glucose filtered by the glomeruli. 90% of the glucose reabsorption
occurs through SGLT 2
o Inhibition will result in glucose excretion of only 30-50% of the amount filtered
o Dapagliflozin, canagliflozin, empagliflozin, ipragliflozin
- Loop Diuretics
o Selectively inhibit NaCl reabsorption in the TAL
o Furosemide, Ethacrynic Acid, Bumetanide, Torsemide
- Thiazide Diuretics
o Inhibit NaCl rather than NaHCO3 that their action is predominantly in the PCT
o Hydrochlorothiazide, chlorothiazide, hydroflumethiazide, Indapamide, methylchlorthiazide, metolazone,
polythiazide, quinethazone, trichlormethazide
- Potassium Sparing Diuretics
 o Preven K+ secretion by antagonizing the effects of aldosterone in collecting tubules. Inhibition may occur by
direct pharmacologic antagonism by mineralocorticoid receptors or by inhibition of Na+ influx through ion
channels on the luminal membrane
o Blunt Na+ uptake and Na+/K+ ATPase in collecting tubules and increase GFR through its vascular effects
o Nesaritide increases GFR and blunts Na+ reabsorption in both proximal CT and collecting tubules
- Osmotic Diuretics
o PCT and descending limb of Henle are freely permeable to water. Any osmotically active agent that is filtered by
the glomerulus but not reabsorbed causes water to be retained in these segments and promote water diuresis
o Mannitol
Proximal Tubule
Proximal Convoluted Tubule
Enzyme Transport Substances Paracellular Transcellular Water Permeability Organic Acid Secretory System
System Reabsorbed Pathway Pathway
Carbonic Na+ / H+ NaHCO3 – 85% K+ H2O – mediated Very High Middle third of the straight part
anhydrase exchanger NaCl – 66% Na H2O – mediated by claudin 2 (S2)
Na+ / K+ Glucose – all by aquaporin-1 - Uric acids
ATPase Amino Acids – (AQP1) - NSAIDs
all - Diuretics
Organic Solutes - Antibiotics

S1 and S2
- Creatinine
- Choline
- Proximal tubule empties to → thin descending loop of Henle
-

Loop of Henle
Transport Substances Paracellular Water Permeability Solute permeability
System Reabsorbed Pathway
Thin Ascending - - - Relatively Permeable
impermeable
Thin Descending - - - Water Permeable -
Limb extraction
Thick Ascending Na+ / K+ / 2Cl- NaCl – 25% - 30% Excess K+ inside Major site of Nearly impermeable -
(diluting cotransporter the cell = salt
segment) (NKCC2 / Magnesium reabsorption
NK2CL) Calcium
- PCT → thin descending → thick ascending

Distal Convoluted Tubule

Hormone Transport System Substances Reabsorbed Water Permeability
Na+ / Cl- cotransporter (NCC) NaCl – 10% Relatively impermeable
Parathyroid Hormone Na+ / Ca2+ exchanger Ca2+
- PCT → thin descending → thick ascending → DCT

Collecting Tubule System

Substances Transport System Principal Cells Hormone Intercalated Cells Water Permeability
Reabsorbed
NaCl – 2-5% (final Epithelial Na channel (ENaC) aldosterone H+, HCO3 Absent ADH
site) Na+ / K+ ATPase Na reabsorbed - Impermeable
K+ channel K secreted - More concentrated
water urine
transport
- PCT → thin descending → thick ascending → DCT → Collecting Tubule System → Renal Pelvis and Ureter
- Determine the final concentration of Na+ in the urine
- Mineralocorticoids exert a significant influence
- Important site of K+ secretion by kidney
- All diuretic-induced changes in K+ balance occur

2. Electrolyte effects of Diuretic Agents

-

3. Therapeutic Uses, Adverse Effects, Contraindications

Drugs Therapeutic Uses Adverse Effects Contraindications

Acetazolamide Glaucoma Hyperchloremic Metabolic contribute to the

Urinary Alkalinization Acidosis development of
Metabolic Alkalosis Renal Stones hyperammonemia and
Acute Mountain Sickness Renal Potassium Wasting hepatic encephalopathy
adjuvants in the treatment Large Doses: in patients with
of epilepsy - Drowsiness, cirrhosis.
hypokalemic periodic paresthesias
paralysis Nervous system toxicity
CSF leakage caused by Hypersensitivit reactions
 trauma or idiopathic - Fever, rashes, bone
Hyperphosphatemia marrow suppression,
intestinal nephritis

dapagliflozin, third-line therapy for Average weight loss

canagliflozin, diabetes mellitus Drop in systolic BP
empagliflozin, urine sodium and
and ipragliflozin urine potassium excretion
increased
Acute Kidney Injury
low incidence
of hypoglycemia
increased incidence of
genital fungal infection in
women
UTI

Bumetanide acute pulmonary edema Hypokalemic Metabolic patients who are

Ethacrynic acid Hyperkalemia Alkalosis sensitive to other
Furosemide Acute renal failure Ototoxicity sulfonamides
Torsemide Anion overdose Hyperuricemia dangerous in hepatic
Hypomagnesemia cirrhosis, borderline
Allergic reactions renal failure, or heart
failure.

nsaids

Bendroflumethiazide hypertension, Hypokalemic Metabolic cirrhosis, borderline

Chlorothiazide heart failure Alkalosis renal failure, or heart
Chlorthalidone1 nephrolithiasis due to Impaired Carbohydrate failure
Hydrochlorothiazide idiopathic hypercalciuria Tolerance
 Hydroflumethiazide nephrogenic diabetes Hyperlipidemia
Indapamide1 insipidus Hyponatremia
Methyclothiazide Impaired Uric Acid
Metolazone1 Metabolism and Gout
Polythiazide Allergic Reactions
Quinethazone1 Weakness, fatigability, and
Trichlormethiazide paresthesias, impotence
acute angle-closure
glaucoma from
hyponatremia

spironolactone, Mineralocorticoid excess or Hyperkalemia chronic renal

eplerenone hyperaldosteronism Hyperchloremic Metabolic insufficiency
amiloride, slow the progression of Acidosis liver disease
triamterene albuminuria in diabetic Gynecomastia CYP3A4 inhibitors = inc
ularitide patients Acute Renal Failure levels of eplerenone
reduce myocardial perfusion Kidney Stones
defects after myocardial
infarction
Liddle’s syndrome
nephrogenic diabetes
insipidus
Mannitol Reduction of Intracranial and Extracellular Volume
Intraocular Pressure Expansion
Dehydration,
Hyperkalemia, and
Hypernatremia
Hyponatremia
Acute Renal Failure

4. Why furosemide is considered a powerful diuretic. MOA?

- Because of the large NaCl absorptive capacity of this segment and the fact that the diuretic action of these drugs is not
limited by development of acidosis, as is the case with the carbonic anhydrase inhibitors, loop diuretics are the most
efficacious diuretic agents currently available..
- acts promptly even in patients with poor renal function or lack of response to other diuretics
- unlike thiazides , loop diuretics increase the Ca2 concentration. In patients with normal Ca2 serum, hypocalcemia does not
result, because Ca2 is reabsorbed in the distal convoluted tubule
- rapidly absorbed therefore useful in emergency situations
Duration of action: 2-3hrs
MOA: Loop diuretics inhibit NKCC2, the luminal Na+/K+/2Cl− transporter in the TAL of Henle’s loop. By inhibiting this
transporter, the loop diuretics reduce the reabsorption of NaCl and also diminish the lumen-positive potential that comes
from K+ recycling

5. loop diuretics cause an increase in Mg2+ and Ca2+ excretion. Prolonged use can cause significant hypomagnesemia. renal
reabsorption of Ca2+ can be increased, loop diuretics do not generally cause hypocalcemia