B: 21-24 Flashcards
Dyslipidemia drugs
Atorvastatin
Rosuvastatin
Simvastatin
Ezetimib
Fenofibrate
Colesevelam
Evolocumab, Alirocumab (PCSK9 Inhibitor= inhibits degredation of LDL-R )
Statins MOA
HMG-CoA reductase inhibitors which is the rate limiting step of endogenous cholesterol synthesis
Statins actions
Liver cholesterol ↓
LDL-R expression ↑ (liver compensation to clear LDL, vLDL remnants from blood)
HDL ↑ 5-15%
Plasma LDL ↓ (20-50% reduction)
VLDL synthesis by liver ↓
Plasma TG ↓
Atorvastatin
Rosuvastatin
Simvastatin
Difference
Atorvastatin: Active as given
Rosuvastatin: Active as given
Simvastatin: Prodrug
Atorvastatin
Rosuvastatin
Simvastatin
Metabolism
CYP450
Atorvastatin
Rosuvastatin
Simvastatin
Indications
Atherosclerotic vascular disease
Acute coronary syndrome
Reduced risk of cardiovascular disease
Reduced mortality in ischemi heart dieseas
Statins side effects
Hepatotoxicity
Myalgia
Rhabdonyolysis
increase creat kinase in 10%
allergy “statin intolerance”
Statins contraindications
Teratogenic
Liver diseas caution
food which inhibit CYP450 eg grapefruit increase hepatotoxicity risk and myopathy.
Colesevelam MOA
resin
Bile acid binding resin are
Large non absorbable polymers that bind bile acid and prevent their absorption in intestine –> increase BA in intestiine > GI side effect
this divert hepatic cholesterol to the synthesis of new bile >> decreasing cholesterol in tightly regulated pool
Bile acid sequestrans drug
Colesevelam
colestipol
cholestyramine
Colesevelam how to give and when?
Oral
With meals
Dont give togather with other drugs (warfarin, thiazide, digoxin, aspirin, statin) and vitamins (K, folate) (wait btw. 4 h)
Colesevelam indications
Primary hypercholesterolemia type IIA (LDL↑)
With Statins
pruritis
Colesevelam side effects
VLDL ↑
TG ↑
- GI: bloat, constipation, diarrhea , Vit. ADEK malabsorption
- Hyperglycemia
- Gall stones
Sterol absorption inhibitors
Ezetimibe
Ezetimibe MOA
decrease intestinal absorption by
Block NPC1L1 in intestine
Reduce cholesterol absorption
Liver cholesterol ↓
LDL-R expression ↑
Plams LDL ↓ (20% reduction)
5% increase HDL
PCSK-9 inhibitors
Evolocumab, Alirocumab (PCSK9 Inhibitor= inhibits degredation of LDL-R )
Humanized monoclonal antibody against enzyme PCSK-9, which normally transport LDL-R to lysosomal degradation
- decreases LDL-R recycling > increase in LDL-R > Decreased LDL
se: Local rxn at site of injection, URT (flu-like symptoms)
Alirocumab, Evolocumab
indications
PCSK-9 inhibitors
- familial hypercholestermeia
- resistant hypercholesteremia
- statin intolerance
Carbonic Anhydrase inhibitors
Acetazolamide
Brinzolamide
Dorzolamid
Methazolamid
Acetazolamide indicaitons
- Diuretic use if edema+ metabolic alkalosis
- Glaucoma (topical brinzolamid, dorzolamid)- decreases secretion of H2CO3 by ciliary epi into aquous humor > decreases IOP
- Mountain sickness: decreases H2CO3 secretion into CSF pro by choroid plexus >> acidosis of CSF> Hyperventilation which protect against high alititude sickness
Innr ear disorder Urinary alkalosis (alkalinization of urine --\> ppt Ca salt --\> renal stones
Acetazolamide side effects
Metabolic acidosis Renal stones (due to urine alkalinization)
Rapid tolerance ( 1 week application only)
Renal K+ wasting
paraesthesia
Hyperammonemia in cirhosis ( due to urine alkalinization prevents NH3 > NH4+ > hepatic encephalopathy)
self-limiting diuresis in 2-3 days
Loop diuretics MOA and names
Furosemide
Torsemide
Ethacrynic acid
Inhibition of Na/K/2Cl in the thick ascending limb
Inhibition of Na/K/2Cl in the thick ascending limb will cause
Loss of NaCl
Loss of luminal positive potential (Mg,Ca reab.↓)
K and H wasting
Hypokalemic metabolic alkalosis
XOX-2 ↑ → GFR ↑
Furosemide drug interactions
NSAID’s (Decreases efficacy )
Aminoglycosides (ototoxicity)
Lithium
Digoxin
How are they different?
furosemide
ethacrynic acid
Furosemide is a Sulfa drug
Ethacrynic acid is not a Sulfa drug
BOTH are loop diuretics
Furosemide indications
- HF
- pulmonary edema
- other forms of edema
- Severe hypercalcemia
HTN
Acute renal failure management
Furosemide side effects
Sulfa drug
Hypovolemia
Hypokalemic metabolic alkalosis
Ototoxicity
Hypocalcemia
Hypomagnesemia
Hyperuriceria
Thiazides diuretics MOA
Inhibition of Na/Cl transporter in the distal conv. tubule
Hydrochlorothiazide drug properties
Sulfa drug
Oral
6-12 h
Hydrochlorothiazide drug interactions
Digoxin
Avoid in DM
NSAID (efficacy decreased due to inhibition of PG, which are important in maintaining GF)
Gout ( due to hyperuricemia SE)
Hydrochlorothiazide indications
HTN
mild HF
Hypercalciurea w/stones. (Nephrolithiasis)
Nephrogenic DI
Osteoporosis
Hydrochlorothiazide side effects
Sulfa
- Hypokalemic metabolic alkalosis
- Hyponatremia
- Hypercalcemia , Hyperuricemia , Hyperglycemia
-hypomagnesmia
Lithium levels ↑
Thiazides diuretic drugs
Hydrochlorothiazide
Indapamide
chlorothiazide(1957) -parenteral only
chlorthalidone
Indapamide indications
HTN
Can be combined with ACEi
Mannitol
MOA
How to give?
Duration of action
Osmotic diuresis
IV
Short
Mannitol indications
- solute overload in
- rhabdomyolysis,
- hemolysis,
- tumor lysis syndrome
- Acute Glaucoma
- brain edema w/coma
- Intracranial HTN
Mannitol side effects
- hyponatremia followed by Pulmonary edema
- hypernatremia as H2O excreted
- headache
- nausea, vomit
Na imbalance
Acute hypovolemia
ENaC inhibitor
Amiloride
triamteren
Amiloride MOA
How to give?
Duration?
ENaC inhibitor
oral !
12-24 h
Amiloride indications
-Hypokalemia caused by other diuretics
Nephrogenic DM
Liddle’s syndrome
- usually in combo with thiazide (Na/Cl transporter inhibitor)
- (book)
Amiloride side effects
Hyperkalemia
ADH antagonist
Tolvaptan
Conivaptan
Tolvaptan MOA
Receptor preferance
How to give?
Duration?
ADH antagonist
V2-R antagonist
parenteral !!
12-24 h
Tolvaptan indications
SIADH
hyponatremia
Tolvaptan side effects
- infusion site rxn
- demyelination if hyponatremia treated rapidly!!
Polyuria
Thirst
Hypernatremia
Antihistamines
H1-r blockers
Types
1st gen: Diphenhydramine, Promethazine, Dimetindene
2nd gen: Cetirizine, Fexofenadine, loratidine
3rd gen: desloratidine, levo-citrizine
Antihistamines- 1st gen
Diphenhydramine
Promethazine
Dimetindene
Antihistamines- 2nd gen
Cetirizine (zyrtec)
Fexofenadine
loratidine (clarithine)
Antihistamines MOA
H1-R antagonists
Antihistamines- 1st gen
How to give
Duration
Metabolism
Molecule type
Oral, parenteral
4-12 h
CYP450
Lipophilic
Diphenhydramine indications
IgE mediated allergies (hay fever, urticaria, )
Sedative
Antiemetic
Sleep aid
Anti motion sickness
Pregnancy nausea
Acute extrapyramidal symp. (eg. due to antipscychotic)
Diphenhydramine side effects
Sedation
Antimuscarinic : dry mouth, blurred vision)
a-R inhibatory effect: orthostatic hypotension
Interact with alcohol- Sedation: BZD , Alcohol
Promethazine special features
Less anti motion sickness effect
More sedative
More autonomic effect
Dimetindene special features
Treatment of allergic reactions
Minimally cross BBB; milder SE
Antihistamines- 2nd gen
What is special about them?
H1-R antag. at peripheral
No autonomic or anti motion sickness effect
Cetirizine
Fexofenadine
loratidine
How to give
Duration
Metabolism
Molecule type
Oral
12-24 h
CYP450
Less lipophilic
Cetirizine
Fexofenadine
Indications
IgE allergies ( hay fever, angioedema
Cetirizine
Fexofenadine
Side effects
Sedation
Arrhythmias in overdose
When interact with alcohol- Sedation
H2-r blockers
- cimetidine (+weak anti-androgenic effect)
- ranitidine
- famotidine
- nizatidine
Histamine analogue name, moa
- beta-histine dihydrochloride:
- weak H1 agonist
- H3 antagonist
beta-histine indication
- vestibular vertigo
- menieres syndrome (virtigo+hearing loss)
beta-histine MOA
- local vasodialation improves inner ear microcirculation
- dose-depending inhibiting effect in CNS on spike-generation in vestibular nuclei neurons.
beta-histine CI
- peptic ulcer
- never give histamine + antihistamine
