Sketchy Pharma Flashcards
-Autoimmune Drugs -CV/renal drugs -Smooth muscle drugs
What part of the kidney does mannitol act as?
Mannitol = osmotic diuretic
-works at proximal convoluted tubule and descending loop of Henle (both of which are freely permeable to water) to draw water out into the lumen and increase free water removal
Use to draw free water out of the CNS (transiently teat ICP) and eye (decrease intraocular pressure transiently)
General use for cholinomimetics
Cholinomimetics = parasympathomimetics
Stimulate parasympathetic tone: increase gastric motility (use to treat non-obstructive ileus), increase lacrimation and salivation (tx Sjogrens), decrease intraocular pressure (use pilocarpine in glaucoma)
What lab value must be monitored in 75 yo F on Bosentan for pulmonary HTN
Bosentan = endothelin antagonist that can cause fatal hepatotoxicty
Monitor monthly LFTs
Main beta2 adrenergic effect
Beta2 activates Gs that activates PKA to relax smooth muscle
Relaxes smooth muscles in bronchial tree => bronchodilation
Relaxes smooth muscle in venuoles (vasodilation) => decreased SVR = drop in diastolic pressure
On fat cells activate lipolysis and FA release, promotes gluconeogenesis and insulin release
Describe the effect on BP of
(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Isoproterenol
(e) Epinephrine
BP changes
(a) Phenylephrine (pure alpha1) increases both systolic and diastolic => increases MAP w/o change in pulse pressure
(b) Norepi: alpha1 vasoconstriction => increase in MAP, little beta1
(c) Dobutamine (mostly beta1) is an inoptrope => increases systolic BP, increases MAP but w/ an increase in pulse pressure
(d) Isoproterenol (both beta1 and beta2) decreased MAP b/c of beta2 (decrease SVR) and widened pulse pressure b/c of beta1 (systolic stays relatively unchanged)
- so systolic RTS and diastolic drops, so MAP drops
(e) Epi: dose dependent change in BP
- low dose epi, beta effects predominate: widened pulse pressure (beta1 increases systolic, beta2 drops diastolic)
- high dose, alpha predominates: vasoconstriction, increased SVR, increase BP
Side effects of ACEi
a) Electrolyte abnormality
(b) Clinically troubling side effect (what bothers the pts
(c) Interaction w/ NSAIDs
ACEi side effects
(a) Hyperkalemia
- ACEi decrease aldo release, aldo generally holds onto Na causing K+ dumping, so w/o aldo we hold onto K+
(b) Persistent dry cough
- avoid this by switching to ARB if it is that troubling to pt
(c) NSAIDs decrease PGE production (PGEs vasoconstrict efferent arteriole) => both NSAIDs and ACEi dilate efferent arteriole (decrease GFR) => using them together can precipitate AKI
- same reason NSAIDs decrease loop diuretic efficacy (inhibit PGE and PGE decrease Na+ reabsorption and increases GFR)
Main indications for the following
(a) oxybutynin
(b) benztropine
Both are antimuscarinics
(a) Oxybutynin works to relax smooth muscle in the ureters and bladder wall to treat overactive bladder
(b) Benztropine is a central M1 antagonist used to treat EPS (symptoms of antipsychotics) and to improve tremor and rigidity in Parkinsons
Which diuretics work at the
(a) PCT
(b) Ascending loop of henle
(c) DCT
(d) CD
Diuretics
(a) Proximal convoluted tubule = acetazolamide, mannitol
(b) Ascending loop of henle = loop diuretics (furosemide)
(c) DCT = thiazides (HCTZ, chlorthalidone)
(d) Collecting duct = K+ sparing diuretics: amiloride, spironolactone
Are thiazides or loop diuretics used for edematous vs. mild HTN?
Thiazides work at DCT (where about 10% of Na is reabsorbed), so much less potent then loop diuretics that work at ascending loop of henle (completely ruins medullary gradient)
=> use loop diuretics for edematous states to get rid of large amounts of excess fluid, while using thiazides for mild HTN
Explain the mechanism of reflexive bradycardia w/ certain sympathomimetics
Sympathetomimetics w/ alpha1 effects (phenylephrine, NE, epi at high doses) cause reflexive bradycardia b/c baroreceptors sense elevated BP and reflexively activate beta tone
Explain the pH disturbance caused by acetazolamide
Acetazolamide = carbonic anhydrase inhibitor, decreases bicarb reabsorption at the proximal convoluted tubule of the nephron
-in exchange you get Cl- in to balance ions
=> results in hyperchloremic non-anion gap metabolic acidosis
Explain how diphenhydramine can be helpful in treating side effects of Risperidone
Diphenhydramine (H1 receptor blocker) is lipophilic => has CNS activity and can help re-establish the dopmaine-cholinergic balance in the brain, therefore helping w/ acute dystonia or other extrapyramidal side effects of antipsychotics
2 side effects specific for Verapamil over other CCBs
CCBs frequent side effects: light-headedness, headache
Verapamil specifically- constipation (literally in 25% of pts) and gingival hypertrophy (ew)
Features of acetylcholinestrase inhibitor overdose
ACh-ase OD = parasympathomimetic OD = symptoms of too much parasympathetic innervation = DUMBBELS
-also caused by organophosphate poisoning
diarrhea urination miosis (pupils constricted) bradycardia bronchospasm lacrimation salivation
Mechanism of nitrates for angina
Be specific- what molecules mediate??
Nitrates: broken down by vascular smooth muscle to release NO. NO then activates guanyl cyclase to increase cGMP. cGMP (key modulator) stimulates dephosphorylation of myosin light chain which stops it from binding to actin => smooth muscle dilation
Venous smooth muscle dilation = decreased preload = decreased LVEDV and myocardial O2 demand
Indications for CCB
(a) First line for stable angina
(b) 2 vasospasm d/o
(c) Neuro ppx
(d) HA
(e) Which for antiarrhtyhmic
Calcium channel blockres
(a) Stable angina use vasodilators (dihydropyridines) to dilate coronary arteries and decrease afterload
(b) Treat prinzmetal angina and Raynaud’s phenomenon
(c) Ppx of vasospasm after subarachnoid hemorrhage (MC 2/2 rupture of berry aneurysm)
(d) Migraine ppx
(e) Non-dihydropyridine (cardiac selective) as anti-arrhythmic
3 contraindications for ACEi
- Hereditary angioedema (C1 estrase deficiency)
- Pregnancy- ACEi is teratogenic
- B/l renal artery stenosis- makes sense here b/c these pts need angiotensin II on board to maintain their GFR
Why do pts on extended release oral nitrates need a daily break?
Pts can develop nitrate tolerance, where vascular smooth muscle beds decrease metabolism to NO (active molecule to increase cGMP and venodilate)
W/ reduced metabolism, pt gets side effects of headaches and flushing, so give daily break from the medication to prevent tolerance build up
Describe the features of atropine overdose
Think of atropine (antimuscarinic) overdose as the opposite of dumbbels
“dry as a bat” (decreased lacrimation and salivation)
“hot as a hare” (can’t lose heat by sweat)
Tachy (can’t slow down HR)
“blind as a bad” b/c antimuscarinics cause mydriasis and cycloplegia (inability to accomodate lens to nearby objects)
“mad as a hatter”
Explain the mechanism by which ACEi help in tx of chronic HF
- ACEi decrease SVR (by causing vasodilation) => decrease afterload
- ACEi cause natruiresis => decreased preload
Mechanism by which nitroprusside is helpful in hypertensive emergency
Nitroprusside is broken down in NO, then NO increases intracellular cGMP which relaxes vascular smooth muscle => vasodilates
Decreases peripheral vascular resistance/afterload
ACEi’s effect on
(a) SVR
(b) GFR
(c) Diuresis
ACEi inhibit conversion of ATI to ATII
(a) SVR decreases b/c blocked vasoconstrictor (ATII vasoconstricts), so decreased afterload
(b) GRF decreased
- ACEi causes vasodilation all around, including vasodilation of efferent arteriole
(c) ACEi cause a natural diuresis
Use of the following antimuscarinic agents
(a) Atropine
(b) Scopolamine
(c) Ipratropium
Muscarinic antagonists = drugs that block muscarinic (parasympathetic) tone
(a) Atropine- reverse lethal bradyarrhtyhmias or AV block
(b) Scopolamine (patch) for motion sickness
(c) Ipratropium/tiotropium: inhaled muscarinic antagonists for bronchodilation and decreased airway secretion in COPD
Best initial HTN agent if pt has concomitant
(a) HF
(b) Diabetes
(c) African American
(d) Edlerly
(e) Previous MI
Try to hit two birds w/ one stone
(a,b,e) If pt has concomitant HF, diabetes, or h/o MI: start w/ ACEi b/c can reduce mortality
(c,d) African Americans and elderly do specifically well w/ CCBs
Why aged cheese and wine can be dangerous to ppl on certain antidepressants
(a) Tx
Aged cheese and red wines contain tyramine which is metabolized by MAO-A (degrades Epi and NE). MAO can be blocked by MAO-inhibitors (class of antidepressants) => tyramine not broken down and goes on to cause hypertensive crisis
(a) Treat this hypertensive crisis w/ phentolamine (nonselective alpha blocker)
Differentiate the two classes of CCB
CCB (all of which block L-type voltage gated calcium channels) divided into
- Dihydropyridine: more selective for smooth muscle in arteries => used as vasodilators
- Nifedipine, Amlodipine, Nicardipine - Non-dihydropyridines: more cardio-selective => best for decreasing HR and contractility => reducing CO and myocardial O2 demand
- Verapamil = most cardiac selective
- Diltiazem = cardiac mostly w/ some vasodilatory effect
Explain beta-blocker use in acute vs. chronic HF
Avoid beta-blockers in acute HF (b/c you need the compensatory tachycardia and inotropy)
But then beta-blockers reduce overall mortality s/p MI and in chronic HF
-potentially 2/2 reduced myocardial oxygen demand, anti-arrhythmic effects, or inhibition of catecholamine-induced remodeling
Which psych drug does thiazide diuretics alter excretion of?
Thiazides decrease the renal excretion of Lithium => be careful of lithium overdose/toxicity in pt on both Li and thiazide diuretics
Name the drug
(a) Alpha-2 agonist for hypertensive urgency
(b) Nonselective alpha-antagonist for cocaine induced HTN
(c) Alpha antagonist for PTSD
(a) Clonidine = alpha2 agonist that reduces BP quickly => use in HTN urgency
(b) Phentolamine = alpha1 and alph2 antagonist given for cocaine induced HTN
(c) Proazosin = alpha-1 selective antagonist that can help w/ the nightmares and sleep disturbance in PTSD
Why are ACEi especially good for pts w/ HTN and diabetes?
ACEi slow the progression of diabetic nephropathy => really good for pts w/ HTN and DM
-also ACEi can be started in a pt w/ borderling high pressures who have albuminuria: albumin (protein) in urine sign of impending nephropathy => want ACEi on board
How do thiazides help in tx of diabetes insipidus?
Thiazides (inhibit NaCl cotransporter at DCT) cause hypovolumeia induced increase in Na and Cl reabsorption in more proximal segments of the nephron
-this helps relieve some of the polyuria seen in nephrogenic DI b/c kidney is less dependent on collecting duct (ADH dependent) reabsorption of solutes/water
How does local phenylephrine act as
(a) Decongestant
(b) Pupillary dilator
(a) Local vasoconstriction in the nasal mucosa (lots of alpha1 receptors there) reduces edema of nasal mucosa
(b) Activates alpha-1 at pupillary dilator muscle => causes mydriasis
Main alpha2 adrenergic effect
Alpha2 = sympatholytic
(thru G1, decreases cAMP)
Decreases nt release (presynaptic inhibition) => decreased BP
Inhibits insulin release and lipolysis
Decreases aqueous humor production (esp. Brimonidine) so can be used for chronic open angle glaucoma tx
Why NSAIDs may reduce efficacy of furosemide
Furosemide inhibits NKCC at ascending loop of henle
PGE enhances furosemide’s effects by increasing GFR (by dilating afferent arteriole) and further reducing Na+ reabsorption
So NSAIDs (inhibit PGE production can interfere w/ loop diuretic efficacy
When combined w/ nitrates, which drug combo has a mortality benefit for diastolic HF pts
Hydralazine (potent arterial dilator) + nitrates (potent venous dilator) has a mortality benefit for diastolic HF
Hydralazine decreases afterload while nitrates decrease preload
Explain how digoxin acts as a inotrope
Digoxin = cardiac glycoside from the fox glove plant, NaK ATPase inhibitor
NaK ATPase inhibited => Na+ not transported out of the cell so intracellular Na increases which stimulates/reverses Na/Ca exchanger
-Na needs to get out of the cell somehow so it exchanges w/ Ca => increased intracellular and SR Ca which increases contractility
Explain use of tamsulosin in older men
Tamsulosin = selective alpha1 blocker- blocks smooth muscle contraction of urethra relieving the urinary retention seen in BPH
Which specific diuretic should be used in the tx of Liddle syndrome
Liddle syndrome = congenital overactivity of ENaC Na+ reabsorption channel in the collecting tubule
Use Amiloride, K+ sparing diuretic that directly inhibits ENaC channels
Which receptors are activated by the following sympathomimetics
(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Isoproterenol
(e) Epinephrine
(a) Phenylephrine = relatively pure alpha1 agonist (all about dat smooth muscle activation/contraction)
(b) NE: Primarily alpha (both alpah1/alpha2), bit of beta1
(c) Dobutamine = mostly beta1 (so increased CO) w/ a little beta2 (decrease in diastolic)
(d) Isoproterenol: both beta1 (HR and contractility) and beta2 (vasodilation- reduced diastolic 2/2 reduced SVR)
(e) Epi: potent beta and alpha, dose dependent
- low dose: beta predominates
- high dose: alpha predominates
Which of the 5 senses may be impaired by furosemide?
Hearing- furosemide can have a dose-dependent ototoxic effect
Misoprostol
(a) Main side effect
(b) Use as ppx
(c) OBGYN use
Misoprostol = PGE1 agonist
(a) Diarrhea b/c of increased gastric activity
(b) Use as ppx for NSAID-induced gastric ulcers b/c PGE1 increases mucin-production by GI tract
(c) Used to stimulate uterine contractions to hasten labor or terminate pregnancy
Digoxin
(a) Predictor of mortality in acute toxicity
(b) GI involvement
(c) Pathognomonic visual feature
Digoxin
(a) Degree of hyperkalemia = predictor of mortality
- recall if Na/K ATPase is inhibited, K+ can’t get into cells => hyperkalemia
(b) N/V/abdominal pain
(c) Color vision changes, xanthopsia = objects appear yellow
Main types of shock treated by
(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Epinephrine
(a,b) Phenylephrine and NE used in hypovolemic, distributive shock (b/c increase SVR/venous return) and septic shock
(c) Dobutamine = inotrope for acute decompensated heart failure or cardiogenic shock
(d) Epi in anaphylactic shock
Main effects of angiotensin II
(a) on GFR
(b) on Na reabsorption
(c) on aldo release
Angiotensin II = potent pressor (vasoconstrictor)
(a) Increases GFR via constriction of efferent arteriole
(b) Works at PCT to increase NaHCO3 reabsorption
(c) Increases aldo release from adrenal cortex
Suffix of
(a) ACEi
(b) ARBs
(c) Benefit of ARBs over ACEi
(a) ‘pril’ = Lisinopril, analapril = ACEi
(b) ‘sartan’ = Losaratn = ARB
(c) Same activity, use ACEi first then use ARB in ppl who can’t tolerate ACEi
- ex: ppl who get persistent dry cough from ACEi
Main indication for digoxin immune FAB
Digoxin immune FAB (antibody) for sympatomatic (aka arrhythmias) digoxin toxicity
-so pt on digoxin has arrhythmia => give Digoxin immune FAB
Danger when first starting ACEi
(a) Why start HF pts on low dose then increase gradually
When first starting ACEi look out for hypotension and syncope
(a) Esp in pts w/ existing HF (already have super high renin) b/c this sudden removal of the pressor effects of ATII can cause dangerous hypotension and syncope
Potential electrolyte abnormalities induced by furosemide
Furosemide inhibits NKCC in the thick ascending loop of henle
- can cause hypokalemia (b/c not reabsorbing K+)
- also can cause hypomagnesemia, b/c inhibiting NKCC reduces the lumen positive pressure that causes excretion of Mg, so furosemide stimulates secretion of Mg
Major thing to avoid when treating cocaine overdose
Mostly symptomatic/supportive therapy
But DONT give beta-blockers, b/c unopposed alpha activity will vasoconstrict and lead to end organ damage
Instead can give phentolamine (alpha antagonist) to reduce BP
Mechanism of cocaine that causes
(a) HTN/tachycardia
(b) agitation/seizures
(c) Nasal septum perforation
Cocaine = inhibits NET and DAT (NE and DA transporters responsible for reuptake of nts by the presynaptic neuron)
(a) Peripheral NET inhibition => increased NE peripherally = increased BP and HR (mainly alpha1)
(b) Central DAT inhibition => arousal, seizures, midriasis (dilated pupils), agitation
(c) Locally increases NE release in the nose = potent vasoconstrictor (alpha1) => ischemia locally
Name some unwanted side effects of diphenhydramine
Diphenhydramine = H1 receptor blocker, lipophilic so crosses BBB
- has some 5-HT receptor antagonist effects => stimulates appetite = weight gain
- antagonizes muscarinic receptors => can cause same pic as atropine overdose: pupillary dilation, urinary retention, dry mouth, constipation, delitium
- also inhibits alpha1 receptors => dizziness and hypotension
Explain why dobutamine is used as a pharmacologic agent for cardiac stress test
Dobutamine = beta1 agonist = Gs receptor to increase intracellular cAMP in cardiac myocytes
-so increases HR and contractility (overall CO) which also increases myocardiac O2 demand => can reveal areas most sensitive to ischemia = use as pharmacologic stress test
Lab abnormalities seen on thiazide diuretics
(a) BMP changes
(b) Lipid panel
Thiazide induced lab abnormalities
(a) Hypokalemia (b/c more Na to the collecting duct, so more K+ pushed out while reabsorbing Na), hyperglycemia (thiazides impede insulin release and tissue glucose uptake)
- hyponatremia
(b) Hyperlipidemia: increase LDL and TG
Indication for a selective NE transport inhibitor
NET inhibitor = Atomoxetine (straterra) = stimulant used to tx ADHD
-NET reuptakes NE at the presynaptic neuron => inhibition increases NE available in the synapse
2 indications of pilocarpine
Pilocarpine = parasympathomimetic
Tx dry mouth and glaucoma
-increases salivary secretions (M3 receptors on glands) and contracts ciliary muscle to increase aqueous humor outflow to high intra-ocular pressure
Go to 3 drug combo for treating primary hypertension
Primary HTN tx: thiazide diuretic (HCTZ) + ACEi (Lisinopril, ARB if dry cough) + CCB (long acting dihydropyridine to vasodilate)
Explain why some women may like spironolactone, and why some males may hate it
Spironolactone (K+ sparing diuretic) inhibits aldo receptor, but also has some cross reactivity, it’s an anti-androgen (both blocks testosterone synthesis and directly antagonizes androgen receptor)
=> spironolactone is used in tx for women w/ PCOS to decrease hirsuitism and symptoms of hyperandrogenism
=> spironolactone can cause low-T => gynecomastia, impotence, decrease in libido in men :-(
Which CCB is safest during pregnancy?
CCB during pregnancy = Nifedipine (dihydropyridine vasodilator)
Main side effects of nitrate therapy
Nitrate side effects: pounding headache, cutaneous flushing, tolerance (decreased metabolism to NO over time causing dizziness/HA- explains the need for daily breaks)
Differentiate Spironolactone and amiloride
Both are K+ sparing diuretics that work at the collecting duct
Spironolactone inhibits the aldo receptor, while amiloride inhibits ENaC (one of the main transporters aldo stimulates)
-but spironolactone is nonspecific => can block androgen receptors and block testosterone synthesis
Amiloride is more specific, doesn’t have any effects on androgens
