Pharmacology Flashcards
is biliary excreted so it is safe for renal impairment patients
indapamide, clopamid, Xipamide
they are Ca channel blockers and Diuretics
Indapamide, Clopamide, Xipamide
is effective in renal impairment if GFR is 20ml/min
Metolazone
short acting thiazide
cloro, Hydrocloro, Hydroflumme, bendroflumme
Long acting thiazide
Cyclo, poly, thriclormethiazide
the only thiazide drug that taken parenteral
chlorothiazide
thiazide taken?
orally
which tubule is thiazide secreted
actively secreted in PCT
antagonized with thiazide diuretic effect
Probenecid
تيته مينفعش تاخد دوا النقرس مع دوا البول
used in nephrogenic diabetes insipidus
thiazide
act as antidiuretic, it increases ADH sensitivity
Therapeutic uses of Thiazide
- Edema (renal, hepatic, cardiac)
- mild to moderate hypertension
- nephrogenic diabetes insipidus
- premenstrual tension and migraine
- Calcinuria, Ca renal stones, hypocalcemia, osteoporosis
Diuretic that is safe to renal impairment patients
indapamide, Xipamide, Chlopamide
Mechanism of Action of Thiazide
1) thiazide actively secreted in PCT ana Probenecid antagonizes its Diuretic effect
2) thiazide act in early part of DCT by inhibiting Na/Cl symporter and reabsorption (only 10% of Na)
3) excess Na reaches late part of DCT which exchanged with K and H
4) the remaining is secreted in urine with water
Results of thiazide in blood
Hypovolemia
Hyponatrimea
Hypokalemia
Hypochloremia
Hypomagnesmia
alkalosis
Hypercalcemia
what happens to thiazide effectivity when GFR less than 20ml/min
losses in diuretic effect
the effect of thiazide in nephrogenic Diabetes insipidus
act as antidiuretic by increase the sensitivity of ADH by the kidney
the effects of the thiazide
- Diuretic effect
- Antidiuretic effect in Diabetes insipidus
- Antihypertensive
- Hyperglycemia
- Hyperlipidemia
- Hyperuricemia
How thiazide make its antihypertensive effect
By its diuretic effect and direct VD
What the thiazide make in VD
- it is a K channel opener that leads to hyperpolarization
- it secretes prostaglandins. NSAIDs decrrease its effect
- it decreases Na load and edema in BV so decreases the effect of adrenaline and angiotensin
how thiazide cause hyperglycemia?
it is a K channel opener and decrease insulin secretion from panceas
How thiazide cause hyperuricemia
it competes with uric acid in secretion
how thiazide is useful in heart failure
it causes diuresis so it decreases reduces return and EDV and decreases preload
It is direct arterial VD thus reduces afterload
Adverse effects of thiazide
- Hypovolemia
- Hyponatremia
- Hypokalemia
- Hypochloremia
- Hypomagnesmia
- Alkalosis
- Hypercalcemia
- hyperglycemia
- hyperlipidemia
- hyperuricemia
- Allergy and cross allergy
- GIT irritation
- Bone marrow depression
- Fetotoxicity
Contraindications of thiazide and frusemide
- hypersensitivity
- Pregnancy
- Gout
- renal and hepatic insufficiency
- Diabetes mellitus
- with digitalis
- with steroids (more worsening of hypokalemia)
causes Hyperammonemia
Acetazolamide
Causes Fetotoxicity
Thiazide and Frusemide
because it passes placenta
Theraputic uses of Acetazolamide
- Edema
- Glucoma
- petit mal epilepsy
- alkalinize urine to dissolve urate stones
- prevention of acute mountain sickness
side effects of Acetazolamide
- weak and self limiting Diuretic
- Allergy and Cross allrgy
- metabolic acidosis
- alkaline urine leads to formation of phosphate stones
- Hepatic encephalpathy in patient with hepatic insufficinecy due to hyperammonemia
- CNS sedation and drowsiness
- Hypokalemia
Sulfonamide derivatives of loop diuretics
Frusemide, Torsemide, Bumetanide
Non- sulfonamide derivatives of loop diuretics
Ethacrynic acid, Idocrinone, Tienilic acid
absorption of loop diuretics
oral and IV
uses extensive plasma protein binding
loop diuretics
where is loop secreted
PCT
Frusemide
oral onset of action …. min and ….. h duration
IV onset of action …. min and …. h duration
30 min – 6 h
2-5 min —– 3h
needs hepatic metabolism
loop
needs hepatic metabolism
loop
Spironolactone
inhibit carbonic anhydrase enzyme
acetazolamide
frusemide
mechanism of action of Fursemide
- fursemide is actively secreted in PCT. Probenecid antgonizes its diuretic effect
- Fursemide has sulfa radical that inhibit carbonic anhydrase enzyme
- Frusemide act in the thick part of ascending loop of Henle by inhibition of symporter Na/k/Cl that disturb countercurrent multiplier system leads to excess water excretion.
- excess Na is go to DCT and some of them exchanged with K and H
- the remaining is excreted with water
effect of loop on blood
- hypovolemia
- hyponatrimia
- hypokalemia
- hypochloremia
- alkalosis
- hypomagnesmia
- hypocalcemia
effective as diuretic even if GFR less than 10 ml / min
Frusemide
has antihypertensive effect: Only by its diuretic effect. No direct VD effect.
Frusemide
actions of Frusemide
diuretic effect
antihypertensive effet
hyperglycemia
hyperlipidemia
hyperuricemia
increase protaglandins secretion
thiazide
frusemide
used in cerebral edema
Frusemide given IV
best in acute heart failure (pulmonary edema)
Frusemide
best in sever or refractory edema
Frusemide»thiazide
Uses of Frusemide
- Edema (pulmonary edema from acute left sided heart failure,, cerebral edema given IV, sever edema)
- hypertension
emergency hypertension and hypertensive encephalopathy by IV
sever or resistant HTN given oral
hypertension with renal impairment - acute renal failure
- Hypercalcemia
- hyperkalemia
used to emergency hypertension as in hypertensive encephalopathy
Frusemide given IV
best in acute renal impairment
Frusemide
used in hypercalcemia
Frusemide
side effects of Frusemide different of thiazide
- hypocalcemia
- renal caliculi
- Nephrotoxicity: intersitial nephritis
- ototoxicity specially in patient with renal impairment or using ototoxic drugs gentamycin
Drug interactions of Frusemide
- warfarin
- lithium carbonate
- Probencid
- NSAIDS
- Aminoglycosides
- Cephalosporins
- Digitalis
have more potent diuretic effect than Frusemide
Torsemide and Bumetanide
has the same efficacy of frusemide, but it has direct VD effect.
Piretanide
non sulfa loops different from frusemide in
- non sulfa ( not inhibit carbonic anhydrase, no cross allergy)
- uricosuric effect
- more irritating to GIT
- cause sever deafness
mannitol is given by
IV
used in acute glaucoma
mannitol
used in increased intracranial tension
mannitol
used in chronic glaucoma
Glycerol
osmotic diuretics
- mannitol
- urea
- glucose
- glycerol
from loop diuretics has uricosuric effect
Ethacrynic acid, indacrinone, tiellnic acid
Aldosterone antagonists
spironolactone and eplerenone
Aldo spiro Eple
Non-Aldosterone antagonists
amiloride and triamterene
source of spironolactone
synthetic
chemistry of spironlactone
steroid
pharmokinetics of spironolactone
- absorbed orally
- converted in liver to canrenone
- delayed onset and long duration
- pass BBB
mechanism of action of spironolactone
antagonizes aldosterone for mineralcorticoid receptors in DCT and collecting ducts leading to inhibition of Na/k exchanger and Na/H exchanger
pharmacological actions of spirono
increase Na, Cl, Ca, water in urine (low efficacy)
k retention leading to hyperkalemia
H retention leading to acidosis and alkalinization of urine
No hyperglycemia
No hyperlipidemia
No hyperuricemia
used in hyperaldosteronism
spironolactone
uses of sprironolactone
achieve synergism by using it with thiazide or loop diuretics to save K
alternatives to thiazide and loop diuretics when the are contraindicated
used in hyperaldosteronism which is either primary conn’s syndrome ore secondary to liver cirrhosis, nephrotic syndrome, and congestive heart
failure
used in conn’s syndrome
spironolactone
causes sexual disturbance
spironolactone
adverse effects of spironlactone
Hyperkalemia specially with renal impairment
acidosis
hypersensitivity reactions
Gut upset: gastritis, diarrhea, gastric bleeding
CNS disturbance: headache, drowsness, confusion
Feminzation (gunecomastia) and impotence in males and irregular menstruation and musculization in females
similar to spironolactone but without sexual disturbance side effects
Eplerenone
Drug interactions of spironolactone
- with thiazide and loop diuretics caues synergism and saves K
- with ACE inhibitors, AT antagonist, b- blocker, NSAID leads to sever hyperkalemia
- Carbenoxolone
used in lithium-induced nephrogenic diabetes insipidus.
amiloride
causes hypersensitivity as photosensitivity
amiloride and triamterene
causes skin rash
spironolactone
adverse effects of non aldosterone antagonizes
- hyperkalemia
- acidosis
- photosensitivity
- Gut upset
- Triamterene causes renal stones and acute renal failure if given with prostaglandins inhibitors as indomethacin
unmask the nephrotoxic effect of triamterene
indamethacin
from acidyfing diuretics
ammonium chloride
causes hyperchloremic acidosis
ammonium chloride
causes acidic urine
ammonium chloride
used as nauseant expectorant
Ammonium chloride
Treat hypocalcemia and tetany
Ammonium chloride
increase excretion of basic drugs as amphetamine and ephedrine
Ammonium chloride
causes acidosis and acidic urine
Ammonium chloride
increase activity of urinary antiseptic such as methenamine
Ammonium chloride
treat tetany
Ammonium chloride
Urine alkalinizers
Na bicarbonate, lactate, acetate
uses of methylxanthine
acute pulmonary edema
action of Theophylline
decrease NaCl reabsorption and increase excretion with water in urine
uses of urine alkalinzers
1- Alkaline expectorants.
2- Treat metabolic acidosis.
3- Alkalinize urine:
a. To increase excretion of acidic drugs as aspirin and penicillin.
b. To relieve dysuria and inhibit growth of E-coli in UTI.
c. To increase activity of sulphonamide and prevent formation of renal
stones by sulfa.
d. To dissolve urate renal stones
help excretion of acidic drugs as aspirin and penicillin
urine alkalinzers (Na bicarbonate, lactate, acetate)
relieve dysuria and inhibit growth of E-coli in UTI.
urine alkalinzers
used as Alkaline expectorants.
urine alkalinzers
To increase activity of sulphonamide and prevent formation of renal stones by sulfa.
urine alkalinzers
causes hepatic encephalopathy
acetazolamide
due to hyperammonemia
Drugs that can cause hyperuricemia
Aspirin: small dose competes with uric acid for acid secretory system.
Diuretics: competes with uric acid for organic acid secretory system.
Alcohol: ↑ urate production (↑nucleotides catabolism) - ↓ urate excretion.
Cytotoxics: ↑ uric acid production (↑ nucleic acid turnover).
xanthine oxidase inhibitors
Allopurinol
Mechanism of Action of colchicine
- Selective inhibitor of microtubule assembly →↓ leucocyte migration & phagocytosis.
- Reduces production of leukotriene B4 (chemotactic for neutrophils).
contraindicated in patients with G6PD deficiency
pegloticase
They are similar to thiazide pharmacologically but differ chemically
with long duration of action
- Chlorothaldione
- Indapamide, Clopamide and Xipamide
- Metolazone
acetazolamide given?
oral, IV, eye drops
f
f
other urine acidifier
Ascorbic acid and methionine
causes Hyperchloremic acidosis
Acetazolamide
ammonium chloride (acidifying diuretic)
uricosuric drugs
Probenecid - Sulfinpyrazone - Benzbromarone
Mechanism of uricosuric drugs
Directly inhibit URAT-1 (a urate-anion exchanger located at the apical brush border of the proximal nephron) and therefore, reduce urate reabsorption
