renal pharmacology 1 Flashcards
function of kidneys - 3
excretion of drugs/ metabolites from body via filtration
maintain volume, pH, electrolytes of extracellular fluid
respond to environmental factors like dietary changes
renal system contains left and right kidney which is linked to ___ via __ and __ linked to __ and __. tubes called ___ feed into bladder, allowing for eventual excretion of urine via ___
circulatory system
renal veins
arteries
aorta
inferior vena cava
ureters
urethra
the kidney recieves ___ of cardiac output
1/4
in the avg adult, kidneys filter ___ a day leading to excretion of ___ per 24hr
120L
1.5L
nephron
functional unit of kidney
filtration, reabsorption, secretion
the nephron’s filtrate does not contain ___
protein
the nephron’s filtrate does not contain protein unless - 2
suffering kidney disease (albumin in filtrate)
infection (bacterial cells can contain protein)
in the nephron, the glomerulus is fixed to the ___, which leads to the ___, which then leads on to the ___, which is surrounded by a capillary network. That feeds into the ____ that then links to the collecting duct.
bowman’s capsule
proximal convoluted tubule
loop of Henle
distal convoluted tubule
podocytes
cells with fingerlike projections that wrap around glomerular capillaries, inc sa to aid filtration
the renal tubule’s ascending limb is impermeable to ____ due to thickness and tight junctions
water
water loss is regulated by 3 hormones -
antidiuretic hormone
aldosterone
renin indirectly
___% of water reaches the collecting ducts
10, most reabsorbed in nephron before then
conditions pertaining to kidney function - many but 6
hypertension
lupus
diabetes
anorexia nervosa
chronic heart failure
kidney disease
hypertension
long term medical condition
blood pressure is elevated in arteries
water retention in response to high Na+ conc
often caused by stress or underlying condition e.g. kidney disease, high salt diet, obesity
often asymptomatic
hypertension is a major risk factor for - 2
stroke and heart disease
e.g. myocardial infarction, inschaemic stroke
what is vasopressin also known as
antidiuretic hormone (ADH)
where is vasopressin secreted
by pituitary gland
where does vasopressin act
on collection tube in nephron to stimulate water conservation by kidneys
how does vasopressin stimulate water consertation by kidneys
binds to V2 receptors on collecting duct
inc Gs, inc cAMP inc aquaporin expression on apical membrane causing osmosis of water into circulatory system from filtrate
inc permeability to water
inc water reabsorption from filtrate into bloodstream
clinical applications of vasopressin - 4
diabetes insipidus
septic shock
post surgery stomach conditions
during abdominal x rays
what drugs inhibit vasopressin - 4
ethanol
lithium
demeclocycline (inhibits vasopressin secretion by tumours)
grapefruit juice
drugs that inhibit vasopressin secretion can cause
nephrogenic diabetes insipidus
nephrogenic diabetes insipidus
failure of renal collecting ducts to respond to vasopressin
vasopressin secretion is enhanced by the drug
nicotine
what is a diuretic
main drug class that alters renal function
prevent body from absorbing sodium
e.g. sodium and alcohol
what are diuretics prescribed for - 6
hypertension
pulmonary oedema
overdose/ poisioning
chronic heart failure
liver disease
kidney disease
what do diuretics do
inc excretion of salt sodium chloride or sodium bicarbonate and water
decrease reabsorption of sodium ions and usually chloride ions
inc the frequency of urination
diuretics admin when
in the morning
direct acting diuretics - 4
loop
thiazide/ thiazide/like
potassium sparing
carbonic anhydrase inhibitors
direct acting diuretics act
directly on the cells of the nephron
direct diuretics act from within ___ and are secreted into the ___ to reach the site of action
tubular lumen
proximal tubule
indirect acting diuretics
osmotic diuretics
modify filtrate contents instead
where do direct acting diuretics target nephron
depends varied on drug type
as diff sites have different levels of sodium reabsorption from urine to blood
which diuretics are the most powerful
loop diuretics
where are loop diuretics absorbed
gi tract
how much filtered Na+ loop diuretics excreted
15-25%
where are loop diuretics site of action
loop of Henle on ascending limb
loop diuretic side effects - 4
excessive urine flow - excessive Na+ and water loss leading to hypovolaemia (low blood vol) and hypotension (low blood pressure)
hypokalaemia (K+ loss) leading to inc risk of drug toxicity esp to digoxin for heart failure
dose related hearing loss at high conc caused by impaired ion transport by membrane in inner ear
idiosyncratic allergic reactions e.g. rashes
clinical applications of loop diuretics - 5
hypertension
chronic heart failure
cirrhosis of liver
nephrotic syndrome
renal failure
(dietary salt restriction)
example of loop diuretics - 2
furosemide
bumetanide
loop diuretics mechanism of action
inhibit Na+/K+/2CL- co-transporter
reducing Na+ reuptake into blood from filtrate/urine
leads to excretion of Na+ and H2O
bartter syndrome type 1
rare autosomal recessive disorder of Na+/K+/2Cl- co-transporter, lacking in function, so similar to diuretic effect
thiazide and thiazide-like diuretics act on
distal convoluted tubule
thiazide and thiazide-like diuretics admin
oral, best absorbed this way
thiazide and thiazide-like diuretics clinical applications - 5
uncomplicated hypertension (if comp use hoop)
reduce heart attack/ stroke risk
severe resistant oedema
prevent recurrent stone formation
nephrogenic diabetes insipidus
thiazide and thiazide-like diuretics examples - 3
bendoflumethiazide
hydrochlorothiazide
chlortalidone
thiazide and thiazide-like diuretics mechanism of action
inhibit sodium and chloride ion co transporters, so excreted into urine with more water
dec blood volume
cause vasodilator effect to reduce blood pressure and inc volume
reduce calcium ion excretion
loop vs thiazide and thiazide-like diuretics advantage of thiazide and thiazide-like diuretics
thiazide and thiazide-like diuretics facilitate calcium reabsorption so better for older patients at risk of osteoporosis
side effects of thiazide and thiazide-like diuretics -5
inc urinary freq
erectile dysfunction
inhibited insulin secretion so impaired glucose tolerance by activation of potassium ATP channels
hyponatraemia - abnormal levels of sodium in blood
idiosyncratic reactions like rashes
coadministration of loop and thiazide diuretic effect
synergistic effect
loop delivers greater fraction of filtered Na+ to site of action of thiazide in distal tubule
what are potassium sparing diuretics also called
aldosterone antagonists
potassium sparing diuretics are __ when used alone
weak
as act on collecting tubule/duct where little sodium reabsorption
potassium sparing diuretics act on
collecting tubule and duct
potassium sparing diuretics clinical applications -5
hypertension
heart failure - prolong survival
conn’s syndrome
low renin hypertension
prevent hypokalaemia (caused by other diuretics)
potassium sparing diuretics examples - 2
spironolactone
eplerenone
what is aldosterone
hormone that conserves Na+ in kidney, salivary glands, sweat glands, colon
influences blood pressure as retains Na+
where is aldosterone secreted
adrenal glands on top of each kidney
potassium sparing diuretics mechanism of action
block distal Na+/K+ exchange
competes with aldosterone for intracellular receptor, inhibiting distal Na+ retention and K+ excretion
at distal site, __% filtered Na+ is reabsorbed
2
spironolactone has a plasma half life of
10 min
spironolactone’s active metabolite is
canrenone
canrenone has a plasma half life of
16 hr
eplerenone has a ___ half life than canrenone
shorter
(has no active metabolites)
side effects of potassium sparing diuretics - 3
hyperkalaemia - so avoid K+ supplements, can cause cardiac arrest
GI upset
spironolactone/ canrenon act on progesterone and androgen receptors too, could cause gynaecomastia (men develop breast tissue) and menstrual disorders in women
carbonic anhydrase inhibitors have a ___ diuretic effect
limited so not rly used
carbonic anhydrase inhibitors ____ excretion of bicarbonate, K+, Na+, water leading an ___ flow of ___ urine
increase
increased
alkaline
carbonic anhydrase inhibitors diuretic example
acetazolamide
carbonic anhydrase inhibitors diuretic clinical applications - 3
prev used as diuretic
glaucoma
infantile epilepsy - anticonvulsant
indirect acting diuretics are __ __ by the nephron, so are pharmacologically __
not reabsorbed
inert
osmotic diuretic is a type of _____
carbonic anhydrase inhibitor diuretic
osmotic diuretics ___ volume of H2O excreted by changing composition of fluid passively, act on __ __ parts of nephron
inc
water permeable
example of osmotic diuretic
mannitol - sweetener in diabetic food, also forces urine prod in people with sudden kidney failure
patient - female aged 83, hypertension, mild osteoporosis. what would u px
thiazide which inhibit calcium ion excretion
loop too powerful for elderly, may be vulnerable to hypotension or hypovolaemia
patient - male aged 56, hypertension, renal failure
loop as helps with renal failure, others too weak
patient - male aged 76, furosemide (loop) for hypertension, has hypokalaemia
potassium-sparing diuretic to help trear hypokalaemia
patient - female aged 37, hypertension, BMI=26.9, no other conditions
lifestyle changes, too young so try first e.g weight loss, dec stress
The kidneys play a significant role in regulating blood pressure through mechanisms such as the
renin-angiotensin-aldosterone system (RAAS)
carbonic anydrase inhibitor mechanism of action
inhibit carbonic anhydrase in proximal conxoluted tubule
reduces reabsorption of bicarbonate, sodium, water
inc bicarbonoate excretion
mild diuretic effect
excessive diuretic use can cause
metabolic alkalosis
diuretic resistance
can be developed in patients with nephrotic syndrome e.g. hypoalbunemia in nephrotic syndrome dec plasma protein binding of loop, dec efficacy
overcoming diuretic resistance
maybe facilitate loop delivery by iv albumin is severe hypoalbuminemia
what is conn’s syndrome
excess aldosterone hormone production from adrenal glands
lupus
a chronic autoimmune disease that causes the body’s immune system to attack healthy tissues e.g. in kidney
anorexia nervosa
inc rate of acute kidney injury and chronic kidney disease, electrolyte abnormalities
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) case study
pt had fatigue, lethargy
hyponatremia (low plasma sodium ion conc)
final diagnosis/ cause - drug induced SIADH due to carbamazepine therapy
personalised med - see prior history
