Antihypertensive Agents

Front 1

Indapamide

Back 1

nonthiazide sulfonamide diuretic:
-both vasodilator and diuretic
-->no reduction in CO

Front 2

time course of diuretic action

Back 2

reduce CO and BV-->incr PVR for 6-8 weeks

then PvR decr, while CO incr

Front 3

Amiloride

Back 3

inhibits SM responses to contractile stimuli, independant of diuretic action

Front 4

Diuretics

Back 4

effective @ lowering BP 10-15 mm Hg
-usually adequate for mile tomoderate essential hypertension

Front 5

Sympathoplegic and vasodilator drugs: effect on bp

Back 5

dimished vascular responsiveness (inflexible tube) --> BP very sensitive to BV
-good to use diuretic

Front 6

thiazide diuretics: target group

Back 6

-mild or moderate hypertension
-normal renal and cardiac function

Front 7

loop diuretics: target group

Back 7

-severe hypertension
-multiple drugs w/ Na-retaining properties
-renal insufficiency (GFR <30 or 40 mL/min)
-cardiac failure or cirrhosis w/ marked Na+ retention

Front 8

K+ sparing diuretics: target group

Back 8

-used when need to avoid excessive K+ depletion (digitalis)
enhance natriuretic effects of other diuretics

Front 9

Diuretics: Adverse effects

Back 9

1) K+ depletion (very bad in those taking digitalis, those w/ arrythmias, in acute I/LV dysfunction) must reduce dietary Na+ (K+ loss coupled to Na+ reabs)

2) Mg2+ depletion
3) impaired glucose tolerance
4) incr. serum lipid conc.
5) incr. uric acid conc.

Front 10

Methyldopa

Back 10

analog of L-dopa:
converted to alpha-methyldopamine and alpha-methylnorepinephrine in CNS
-only antihypertensive effects are on CNS alpha adrenoreceptors

Front 11

Clonidine, Guanabenz, and Guanfacine

Back 11

decreases BP via bradycardia and increased parasympathetic tone (decreases sympathetic tone)
-bind alpha2>>alpha1
(alpha2 on presynaptic adrenergic neurons as well as some post synaptic)
-also act on postsynaptic alpha2 adrenoreceptors to inhibit activity.
-also binds to imidazoline receptor

Front 12

Methyldopa pharmakokinetics

Back 12

enters brain via aromatic amino acid transporter
(maximum effect 4-6 hrs)
-action is based on accumulation of alpha-methylnorepinephrine)
side affects: OVERT SEDATION,
impaired mental concentration, lactation (mediated by inhibition of dopaminergic neurons in hypothalamus)
-positive Coombs test

Front 13

Clonidine

Back 13

reduction of CO (decr HR and relaxation of capacitance vessels), reduction of PVR especially when there is incr sympathetic tone (UPRIGHT POSTURE)

Front 14

Clonidine pharmakokinetics

Back 14

lipid-soluble (readily enters brain)
-given twicea day (short t1/2)
-increasing doses are more effective but also more toxic.

Side Effects: centrally-mediated dry mouth and sedation-if stop get hypertensive crisis(incr. sympathetic tone)
-do not use tricyclic antidepressants
(blocks antihypertensive effects of clonidine)
-do not give to depressed patients

Front 15

Adrenergic neuron-blocking agents

Back 15

prevent normal physiologic release of NE from postganglionic sympathetic neurons

Front 16

Guanethidine
(guanadrel, Bethanidine, debrisoquin)

Back 16

adrenergic neuron-blocking agent
-too polar to enter CNS
-sympathoplegia
-transported across sympathetic nerve membrane by NET, uptake 1
-->replacesNE -->gradual depletion of NE stores in nerve ending
-NEURONAL UPTAKE IS NECESSARY FOR hypotensive EFFECT (cocaine, amphetamine, TCAs, phenothiazines, phenoxybenzamine block effects b/c these block catecholamine reuptake process)
-increases sensitivity to hypertensive efects of exogenously administered sympathomimetic amines (reduced uptake after lon-term guanethidine; and supersensitivity of effector SM cells to sympathomimetic agents)
-may have compensatory Na+ and H20 retention

Front 17

Baroreceptor reflex arc

Back 17

carotid baroreceptors sense decr arterial pressure-->inhibit tonically active neurons in vasomotor center-->disinhibition of sympathetic discharge

Front 18

Guanethidine side-affects

Back 18

delayed or retrograde ejaculation, hypotension, diarreah (increased GI motility due to parasympathetic predominance in controlling GI motility)

Front 19

Reserpine

Back 19

adrenergic neuron-blocking agent
-blocks ability of aminergic transmitter vesicles to take up and store biogenic amines(interferes with VMAT IRREVERSIBLEY)
-depletion of NE, dopamine, and serotonin in central and peripheral neurons
-low doses: decreases CO and PVR
-enters brain readily

Front 20

Reserpine toxicity

Back 20

depletion of cerebral amine stores (parkononism [via dopamine depletion in corpus striatum], sedation, mental depression)
-should not be given to patients with a history of peptic ulcer (produces increased gastric acid secretion)

Front 21

Propanolol

Back 21

beta-blocker
-useful in preventing reflex tachycardia ccaused by direct vasodilators
-decreases CO
-inhibits stimulation of production of renin by catecholamines via beta1 receptors
-resting bradycardia and reduction in HR during exersize

Front 22

Metoprolol

Back 22

-equipotent in inhibiting stimulation of beta1-receptors in heart
-50 to 100 fold less potent thatn propanolol in blocking beta2 receptors
-doesn't exacerbate asthmatics as profoundly as propanolol

Front 23

Pindolol, Acebutolol, Penbutolol

Back 23

-partial agonist: beta blockers w/ some intrinsic sympathomimetic activity
-patients w/ bradyarrythmias
-->decrease HR less thatn other beta-blockers

Front 24

Labetalol

Back 24

hypertensive emergenciesof pheochromocytoma
-alpha and beta blocking effects

Front 25

Carvedilol

Back 25

alpha and beta-adrenoreceptor blocker

Front 26

Prazosin, terazosin, doxazosin

Back 26

selectively block alpha1 receptors on arterioles and venules->less reflex tachycardia
-alpha 1 receptor selectivity-->unopposed negative feedback of NE on its own release via presynaptic alpha2 receptors)-->prevents reflex tachycardia stimulated by beta receptors
-salt retention

Front 27

Hydralazine

Back 27

-vasodilator of ARTERIOLES
-adverse effects: heasdache, nausea, palpitations, sweating, flushing
-slow acetylators: lupus-like syndrome : arthralgia, myalgia, skin rashes, fever

Front 28

Minoxidil

Back 28

Vasodilator of ARTERIOLES
opens K+ cahnnels in SM -->stabilization of membrane @ resting potential-->contraction is less likely
-used in combo w/ beta-blocker or a loop diuretic

Front 29

Sodium Nitroprusside

Back 29

POWERFUL-->dilates veins and arterioles
-activates guanylyl cyclase-->incr cGMP-->VSM relaxation

Front 30

Nitroprusside toxicity

Back 30

-accumulation of Cyanide-->metabolic acidosis, arrythmias, excessive hypotension, death
-give w/ Na thiosulfate as a sulfur donor, helps w/ cyanide metabolism
(could also give hydroxocobalamin)

Front 31

Calcium channel blockers
(verampamil, diltiazem, dihydropiridine family)

Back 31

-inhibition of calcium influx into arterial smooth muscle

Front 32

ACE inhibitors

Back 32

-inhibit converting enzyme peptidyl dipeptidase ACE-->prevents AI-->AII. and prevents hydrolysis of bradykinin
-Enalapril, Captopril, Lisinopril, Benzepril
-decrease PVR (CO and HR are not significantly changed)
-no reflex sympathetic activation
-good for chronic kidney disease: diminish proteinuria and stabilize renal function
(improved intrarenal hemodynamics --> decr glomerular efferent arteriolar resistance--> decreased intraglomerular cap pressure.

Front 33

ACE inhibitors: toxicity

Back 33

-severe hypotension (in hypovolemic)
-acute renal failure (in those w/ stenosis)
-hyperkalemia (renal insufficiency or diabetes)
-dry cough and angioedema(due to bradykinin and substance P)
-contraindicated during 2nd and 3rd trimesters of pregnancy