8 - Pharmacology of AntiHT's Flashcards
What drug based on MOA?
Selectively block a1-adrenoreceptors
@arterioles & venules
↓Arterial pressure
by dilation of resistance/capacitance BVs
Vasodilation –> HypoTensive effect
- *a1-adrenoceptor Antagonists**
- *Prazosin / Terazosin / Doxazosin**
orthostatic hypotension
What drug based on MOA?
**Inhibit NaCl Reabsorption in the DCT** in luminal (urine-side) epithelium
Direct effect:
Block Na+/Cl- Transporter
Enhances Ca2+ Reabsorption
THIAZIDES
Chlorthiazide / HCTZ / Methylclothiazide
Non-thiazide Sulfonamide:
Chlorthalidone / Indapamide / Metolazone
Fenoldopam
Class / MoA / ADR
Parenteral Vasodilator
- *Dilates Arterioles**
- not veins*
D1 Agonist –> also produces natriuresis
↑Intraocular pressure = do NOT use in GLAUCOMA pts
ADRs:
TachyCardia & Provokes ANGINA
What drug based on MoA?
- *Dilates Arterioles**
- no vein effect*
TachyPhalaxis
develops rapidly, limits use in MONOtherapy
Usually used for:
Combination Therapy for Severe HTN
HYDRALAZINE
Oral Vasodilator
may provoke ANGINA
Which Beta Blockers have
Intrinsic Sympathomimetic Activity = ISA
Partial AGONIST @ B2-Ne Receptors
but is overidden by:
B1-NE blockade
ISA BB’s = PAP
Pindolol / Acebutolol / Penbutolol
What drug based on MoA?
- *Dilates Arterioles**
- no vein effect*
Metabolite: opens K+ channels in smooth muscle
of arterioles
Topical
- *MINOXIDIL**
- *Vasodilator**
Used for HAIR GROWTH = Rogaine
- may provoke ANGINA*
- *Headache / Sweating / Hirsutism**
What drug based on MoA?
- *Blocks AT2 Effects**
- antagonism of* AT2 type 1 receptor
- *ARBS**
- artans
NO COUGH, NO EFFECT ON BRADYKININ
clinically similar effects to ACE-i’s
- *ADR’s of BETA BLOCKERS**
- olols
BradyCardia / ↓cardiac contractility & excitibility
CNS = sedation / depression / sleep disturbance
REBOUND SYMPATHETIC STIMULATION
upon abrupt withdrawal = nervousness / tachycardia / HTN
HYPOGLYCEMIA
may exacerbate hypoglycemic episodes in insulin dependent diabetics
BetaBlockers may MASK hypoglycemia in diabetic pts
CCB ADR’s
- *CARDIAC DEPRESSION**
- *Greater in Non-DHP’s (Verapamil/Diltiazem)** > DHP’s (amlodipine)
- *BradyCardia / AV block / HF**
Short Acting Nifedipine = ↑risk of MI –> use LONG ACTING
Dizziness / Constipation / Peripheral Edema
FLushing / Nausea
Diazoxide
Class / MoA / ADR
Parenteral Vasodilator
- *Dilates Arterioles**
- not veins*
Opens K+ channels = stabilize smooth muscle membranes of arterioles
ADRs:
TachyCardia & Provokes ANGINA
Which Beta Blockers have
a-NE-blocking Activity
Stereoisomers have BOTH:
B-NE & a-NE antagonist activity
LABETOLOL
CARVEDILOL
What drug based on MOA?
Inhibits synthesis of AT2
↓vasoconstrictor activity
↓aldosterone release –> Na+ & H2O Retension
Blocks breakdown of BRADYKININ
↑bradykinin = vasoDilation
↓PVR
ACE INHIBITORS
↓BP by ↓PVR
CO & HR are UNCHANGED
no reflex tachycardia
ADRs of ARBS
- *similar to ACE-inhibitors**
- EXCEPT FOR:*
- *COUGH_ & _ANGIOEDEMA**
What drug based on MOA?
Direct agonist of a-adrenoreceptors @medulla:
↓sympathetic outflow / ↓BP / ↓Bradycardia
↑ParaSympathetic Tone
Initially, ↑BP
- > due to stimulation of peripheral a-receptors on arterioles
- when given IV = transient vasoconstriction*
- *CLONIDINE**
- *Guanzbenz** & Guanfacine
CNS-Acting Sympathoplegics
Special Uses for
BETA BLOCKERS w/ ISA
ISA BB’s = PAP
Pindolol / Acebutolol / Penbutolol
↓PVR –> ↓BP
LESS depression of CO & HR
due to greater B2 agonist > B2 antagonist activity
Useful in pts with:
Bradyarrhythmias & Peripheral Vascular Disease
do NOT use in patients with ANGINA
What drug based on MOA?
In brain:
a-methyl-NE –> stimulates post-synaptic a-adrenoreceptors
↓PVR ~↓CO
↓Sympathetic Outflow
- in periphery:*
- *a-methyl-NE replaces NE stores** as false transmitter
- not responsible for antiHTN action*
METHYLDOPA
CNS-acting Sympathoplegics
What drug based on MOA?
Taken up into pre-synaptic NE vesicles –> REPLACES NE
_*Inhibits release of* NE_
@ postganglionic sympathetic effector site on BV
= VASODILATION
- *Guanethidine**
- *Adrenergic Neuron Blocker**
more potent vs Reserpine
- *SEVERE HTN**
- many drug interations*
Impairs baroreceptor reflex –> orthostatic hypotension
ADR’s
THIAZIDES
Chlorthiazide / HCTZ / Methylclothiazide
Non-thiazide Sulfonamide:
Chlorthalidone / Indapamide / Metolazone
HypoKALEMIA
HyperUricemia
gout
HyperGlycemia & HyperLipidemia
<15% increase in serum cholesterol & LDL
ADR’s
CNS-Acting Sympathoplegics
Methyldopa / Clonidine
Guanfacine / Guanabenz
Dry Mouth + Sedation
SUDDEN WITHDRAWAL –> SEVERE HTN CRISIS
if after chronic use
Due to: Rebound sympathetic activity
dose should be TAPERED OFF
Compelling Indications for
ACE INHIBITORS
HF** / **Recent Strole
use with DIURETICS
Post - MI
Diabetes
CKD
What drug based on MOA?
INHIBITION of CA++ Influx
into smooth muscle of arterioles
↓PVR
More Cardiac Depressant activity vs counterpart
↓Conduction thru AV Node
↓HR –> ↓Cardiac Output
Negative Inotropic Effect
- *Non-DHP Calcium Channel Blockers**
- *Verapamil > Diltiazem**
Vasodilator
More cardiac deppressant vs DHP’s
Sodium Nitroprusside
Class / MoA / ADR
Parenteral Vasodilator
Dilates Arterioles & VEINS
Potent –> used for HYPERTENSIVE EMERGENCIES
ADRs:
Accumulation of CYANIDE
TachyCardia & Provokes ANGINA
What drug based on MOA?
Blocks uptake of: NE / DA / 5-HT into pre-synaptic vasicles
depletion of NE stores –> inhibit release of NE
@ post ganglionic sympathetic effector site on BVs
= VASODILATION
- *RESERPINE**
- *Adrenergic Neuron Blocker**
Mild-Moderate HTN
may cause PARKINSONISM = DA depletion
Impairs baroreceptor reflex –> orthostatic hypotension
Ace Inhibitor ADRs
Acute RENAL failure
HYPERkalemia
more likely w/ renal insufficiency / diabetes
due to inhibitory action on aldosterone secretion
AngioEdema
DRY COUGH
- *ASPIRIN + NSAIDS**
- may diminish HypoTensive response*
- *PREGNANCY WARNING**
- contraindicated during 2nd & 3rd trimesters*
What drug based on MOA?
Primarily: ↓CO
Kidneys:
antagonize renin production
Peripheral sympathetic neurons on BVs:
antagonize pre-synaptic B-adrenoceptors = vasodilation
unlikely brain effects:
- *BETA BLOCKERS**
- *-OLOLS**
Non Selective = NPC
Propranolol / Naldolol / Carteolol
Selective B1 = BBEAM
Bisoprolol / Betaxolol / Esmolol (IV) / Atenolol / Metoprolol
What drug based on MOA?
Inhibition of Na+ influx through ion channels
@late DCT & collecting tubule
(luminal = urine-side)
K+-Sparing Diuretic
inhibit Na+ influx in distal & collecting tubules
Triamterene + Amiloride
avoids K+ depletion, of Thiazides
ENHANCES natriuretic effect of other diuretics
CNS-Acting Sympathoplegics
USES
Methyldopa / Clonidine
Guanfacine / Guanabenz
↓Sympathetic nervous system OUTFLOW from brain
Moderate HTN
Intact barorecetor reflex
advantage = low orthostatic HTN
What drug based on MOA?
INHIBITION of CA++ Influx
into smooth muscle of arterioles
↓PVR
Reflex sympathetic Activation –> TachyCardia
↑HR –> ↑CO
- *DHP Calcium Channel Blockers**
- *Amlodipine / Nifedipine / Felodipine**
Vasodilator
less cardiac depression vs NON-DHP’s
What drug based on MOA?
Block Aldosterone receptors
@ late DCT
- *K+-Sparing Diuretic**
- *ALDOSTERONE ANTAGONIST**
Spironolactone + Eplernone
avoids K+ depletion, of Thiazides
ENHANCES natriuretic effect of other diuretics
Thiazide Uses
Chlorthiazide / HCTZ / Methylclothiazide
Non-thiazide Sulfonamide:
Chlorthalidone / Indapamide / Metolazone
Most Frequently prescribed diuretic class
Mild-Moderate Essential HTN
w/ normal cardiac & renal fxn
Lower Doses = similar antiHT action vs higher doses
Higher doses = MORE NATRIURETIC effect
Which drug have a COMPELLING INDICATION for:
POST MI
HIGH CORONARY RISK
HEART FAILURE
- *BETA BLOCKERS**
- olols
What Drug based on MOA?
Inhibits action of RENIN
Angiotensinogen –/–> Angiotensin 1
↓AT1
↓AT2
↓Aldosterone
Direct RENIN Inhibitors
ALISKIREN / REMIKIREN
Diuretics as AntiHypertensives
Clinical Effects
Thiazide + K-sparing Diuretics
- *BP = CO** x PVRCO = HR x SV
- *P**eripheral Vascular Resitance
Initially diuretics (ACUTE):
↓Blood Volume ↓CO , while ↓Na+ stores,
↑PVR may increase
After 6-8 weeks:
Na+ depletion –> ↓PVR
and CO returns to NORMAL
Compelling Indications for ARBS
CKD
DIABETES
