High-Yield Terms to Learn

Baroreceptor Primary autonomic mechanism for blood pressure

homeostasis; involves sensory input from carotid sinus
and aorta to the vasomotor center and output via the
parasympathetic and sympathetic motor nerves.

Catecholamine reuptake Nerve terminal transporter responsible for recycling

pump (norepinephrine norepinephrine after release into the synapse
transporter [NET])

Catecholamine vesicle Storage vesicle transporter that pumps catecholamine

pump from neural cytoplasm into the storage vesicle; also
called vesicle monoamine transporter (VMAT)

End-organ damage Vascular damage in heart, kidney, retina, or brain

Essential hypertension Hypertension of unknown etiology; also called primary

hypertension

False transmitter Substance, for example, octopamine, stored in vesicles

and released into synaptic cleft but lacking the effect of
the true transmitter, norepinephrine

Hypertensive emergency An accelerated form of severe hypertension associated

with rising blood pressure and rapidly progressing
(“malignant damage to vessels and end organs. Often signaled by
hypertension”) renal damage, encephalopathy, and retinal
hemorrhages or by angina, stroke, or myocardial
infarction

Orthostatic hypotension Hypotension on assuming upright posture; postural

hypotension
 SYMPATHOPLEGICS

▪ plegia – paralysis

▪ drugs that block the sympathetic

A. CENTRALLY ACTING

SOA: vasomotor center in the brainstem

▪ Presynaptic α2 agonist → decrease NE release

▪ If bind in postsynaptic α2 receptor the effect is vasoconstrictor (initial effect of CA)

DRUGS: Methyldopa, clonidine, guanabenz, guanfacine

Methyldopa (L-α-methyl-3,4 dihydroxyphenyalanine) – analog of L-DOPA

α-methyldopamine and α-methylnorepinephrine (false neurotransmitter)

effective against at the adrenoceptors that mediate peripheral sympathetic constriction

of arterioles and venules

EFECT: lowers BP by decreasing PVR, HR and CO

▪ Usual dose of methyldopa: maximal antihypertensive effect in 4-6 hours

▪ Effect can persist for up to 24 hours

SIDE EFFECTS

1. Sedation (methyldopa) – onset of methyldopa

2. Lactation associated with increase prolactin secretion can occur both in men and
in women treated with methyldopa

3. False positive Coomb’s test for hemolytic anemia

4. Autoimmune hepatitis

5. Sodium and water retention

CLINICAL USE

1. Used to treat HTN in pregnant women because it does not harm the fetus

CLONIDINE

▪ Most closely resembles to methyldopa

▪ Binds to imidazoline receptors (immediate antihypertensive effects)

EFFECTS:

▪ decrease CO due to decrease HR, decrease capacitance, decrease PVR

▪ reduce blood pressure in supine position

✓ Transdermal preparation will decrease BP for 7 days after single preparation

(less sedation than tablets)

CLINICAL USE

1. Treatment of hypertensive urgencies (not recommended for chronic treatment)

SIDE EFFECTS

1. Rebound hypertension

Treatment: Labetalol, Na nitroprusside – HTN urgency)

2. Dry mouth and sedation

DI: concomitant use of TCA may block the antihypertensive effect of clonidine due to
α-adrenoreceptor blocking action of TCA
B. PERIPHERALLY-ACTING

▪ Adrenergic neuronal blockers

RESERPINE (Rauwolfia serpentina)

MOA: depletes NE and blocks transport of NE into its storage vesicles.

NE

Presynaptic neuron

NE

Vesicular storage protection against metabolizing enzyme

ADR:

1. depression (decrease 5HT (5- Hydroxytryptamine)

2. sodium and fluid retention

3. parasympathetic effects (nasal congestion, acid secretion, diarrhea, bradycardia,

gastrointestinal cramps)
CI: peptic ulcer

B. GUANETHEDINE, GUANADREL, BRETYLIUM

MOA: inhibits of release (exocytosis) of NE

NE

NE

Guanethidine

▪ Long ½ life (5 days) – maximal effect in 1-2 weeks

S/E:

1. Symptomatic postural hypotension

2. Diarrhea

3. Impaired ejaculation

DI: when TCA is administered to patient taking guanethidine, the drugs

antihypertensive effect is attenuated and severe HTN may follow.

I. GANGLIONIC BLOCKER

a. Hexamethonium, mecamylamine, trimethaphan

▪ Block ganglia without prior stimulation

▪ Rarely used due to lack of selectivity (no longer used)

A/E:

1. Excessive orthostatic hypotension

2. Sexual dysfunction

3. Constipation, urinary retention, glaucoma, blurred vision, dry mouth.

II. α-BLOCKERS

SELECTIVE α1-blockers: Doxazosin, Prazosin and Terazosin

▪ not recommended for the initial treatment of high blood pressure

▪ adjunct to other drugs if BP is not adequately controlled (Phentolamine +

Propranolol)

CU: Management in HTN with BPH (benign prostatic hyperplasia)

S/E:

1. orthostatic hypotension (dizziness, syncope)

SYNCOPE: a temporary loss of consciousness usually related to insufficient blood flow

to the brain. It is also called fainting or “passing out”. It most often occurs when blood
pressure is too low (hypotension) and the heart doesn’t pump enough oxygen to the
brain.

2. First dose “SYNCOPE” – initial administration.

NOTE: α1 blocker evoke reflex tachycardia of sympathetic nervous system. It may

cause increase heart rate, contractile force and circulating NE level so it may lead to
myocardial oxygen requirement.

How to counteract?

1. Give the first dose at bedtime and give only ½ or ¼ of the usual dose

2. Hold the diuretics for a day.

NONSELECTIVE: Phenoxybenzamine, Phentolamine

USE: pheochromocytoma (tumor with catecholamines), BPH, urinary retention

C. VASODILATORS

ARTERIOLAR VASODILATORS: Minoxidil, Diazoxide, Hydralazine

MOA: act by relaxing the smooth muscle of the blood vessel, mainly arteries

EFFECT:

▪ Decrease PVR = decrease BP but sodium and water were retained resulting in
peripheral edema → diuretics can be given to decrease the edema

▪ Vasodilators promote an increase in blood flow to brain and kidneys

S/E:

1. Peripheral edema

2. Reflex tachycardia (beta-blockers can be given with AV to decrease the heart rate.

Hydralazine

CU:

1. Management of HTN crisis for pregnant women

2. Adjunct in the management of CHF (Hydralazine + ISDN {Isosorbide dinitrate

“ISORDIL])

Hydralazine should be avoided or use with caution in patients with ischemic heart
disease because the reflex tachycardia caused by Hydralazine can precipitate angina.

S/E: SLE – like Syndrome (HIPS: Hydralazine, INH, Procainamide, Sulfonamide)

Minoxidil

MOA: stimulates outward K+ conductance

Potassium channel opening

Hyperpolarization

Relaxation
 ↓

Venodilation

CU:

1. Management pf hypertensive crisis

2. Hair growth stimulant (used for the treatment of alopecia [baldness]

BN: Rogaine

S/E:

1. Hypertrichosis

Precaution: the dose should not be abruptly withdrawn to avoid rebound

hypertension

Rebound hypertension occurs when blood pressure rises after you stop taking or
lower the dose of HTN drug

DIAZOXIDE

▪ (thiazide – like)

MOA: same with minoxidil

CU: for the management of HTN crisis

S/E: HYPERGLUC

MIXED ARTERIOLAR AND VENODILATOR

SODIUM NITROPRUSSIDE

MOA: stimulates nitric oxide synthase responsible for the synthesis of NO (nitric
oxide) which stimulates guanylyl cyclase

guanylyl cyclase

GTP cGMP (vasodilation)

GTP (Guanosine-5-triphosphate)

CU: management of hypertensive crisis (first line)

✓ Should be freshly prepared and consumed within 24 hours

✓ Prone to photodegradation (inactivated by light)

 - Light-sensitive to prevent degradation to CN-

✓ The IV bottle of bag must be wrapped with aluminum foil or another opaque
material to protect the solution from degradation.

✓ Faint brown tint is typical, blue or brown discoloration of the solution indicates
degradation and the solution must be discarded.

▪ Maximum duration of infusion:

✓ Maximum dose = 10mcg/Kg/min within 10 minutes of infusion
✓ Lower dose = <2 mcg/Kg/min within 72 hours

SIDE EFFECTS

1. accumulation of cyanide (metabolic acidosis, profound hypotension, dizziness and

vomiting)

Remedies: amyl nitrite is used until IV (Na nitrite) and Na thiosulfate can be
administered

✓ thiosulfate is then administered to convert cyanide to inactive thiocyanate

D. CALCIUM CHANNEL BLOCKERS

MOA: blocks the calcium ion channel in the plasma membranes of SM

EFFECTS:

▪ Relax vascular smooth muscles → vasodilation

▪ Increase effect on arteriolar smooth muscles → decrease PVR, decrease CO

▪ Natriuretic effect → decrease BP

TYPES DIHYDROPYRIDINES NONDIHYDROPYRIDINES

Site Blood vessels only Heart and blood vessels
Effect Arteriolar vasodilation Bradycardia and arteriolar
vasodilation
Side effects Reflex tachycardia bradycardia
Drugs Peripheral edema Peripheral edema
-“DIPINES” Verapamil, Diltiazem

Cardiac depressant activity: VERAPAMIL > DIKTIAZEM > DHPs

A. Structure

1. Dihydropyridines (DHP) “DIPINES”

▪ Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, Lercanidipine,

Lacidipine

S/E: Reflex tachycardia, Peripheral edema

2. Non-Dihydropyridines

Verapamil – cardioselective – decrease HR; decrease CO

▪ The most efficacious CCB

▪ Has the greatest depressant effect in the heart

Diltiazem – intermediate action

S/E: bradycardia, peripheral edema

Peripheral edema – accumulation of fluid causing swelling in tissue perfused by the

peripheral vascular system, usually in the lower limbs
B. Based on the Duration of Action

1. Short acting

▪ All NON-DHP (Verapamil, Diltiazem)

▪ All DHP except amlodipine, Lercanidipine, Lacidipine

2. Long-acting

▪ Lacidipine, Lercanidipine, Amlodipine

▪ Not associated with reflex tachycardia

3. Modified long-acting – prepared in modified release

▪ Nifedipine (Adalat GITS), Felodipine (Versant XR, Plendil XR), Verapamil (Isoptin
SR)

▪ Not associated with reflex tachycardia

CU:

1. Alternative in the management of HTN

2. Management of arrhythmia (non-DHPs)

3. Management of angina pectoris (Prinzmetal angina)

Angina pectoris – is the medical term for chest pain or discomfort due to coronary
heart disease. It occurs when the muscle doesn’t get as much blood as it needs. This
usually happens because one or more of the heart’s arteries is narrowed or blocked,
also called ischemia.

Nimodipine

▪ for cerebral vasodilators

▪ treatment of post-surgery in aneurysm (cerebral edema)

Aneurysm – the enlargement of an artery caused by weakness in the arterial wall.

Often there are no symptoms, but ruptured aneurysm can lead to fatal complications.
An aneurysm refers to a weakening of an artery wall that creates a bulge, or
distention, of the artery