Anti Hypertensives- pharmacology

CENTRALLT ACTING
SYMPATHOPLEGICS
 MOA
REDUCE SYMPATHETIC OUTFLOW
FROM VASOMOTOR CENTER BUT
RETAIN OR EVEN INC SENSITIVITY
TO BARORECEPTOR CONTROL
Actions less dependent on posture

METHLY DOPA
 α METHYLDOPAMINE
 α METHYLNOREPINEPHERINE
 ACT ON CENTRAL α
ADRENOCEPTORS

ACTIONS
 REDUCE PERIPHERAL
VASCULAR RRESISTANCE
 VARIABLE RED IN CARDIAC OUTPUT
AND HEART RATE
 DOA: 12-24HR

TOXICITY
 Postural hypotension in vol. depleted pts
 Sedation------at onset
 LONG TERM USE-----persistent mental
lassitude, impaired mental
conc., nightmares, mental depression, extra-
pyramidal signs
 LACTATION—men & women.. Inhib of
dopaminergic mech. in hypothalamus
 POSITIVE COOMBS TEST---hemolytic
anemia , hepatitis & drug fever
 Discont.-----PROMPT REVERS OF
ABNORMALITIES

DRUG INTERACTIONS
 NSAIDS
 SYSTEMIC CORTICOSTEROIDS

CLONIDINE
 α ADRENOCEPTORS IN
MEDULLA OF BRAIN---Sensitizes
vasomotor centers to Inhib by
baroreflexes
 RED. SYMPATHETIC AND INC.
PARASYMPATHETIC TONE
 Nonadrenoceptor site----IMIDAZOLE
RECEPTOR

ACTIONS
 I/V---BRIEF INC IN BLOOD
PRESSURE( PARTIAL α AGONIST)
followed by MORE PROLONGED
HYPOTENTION
 DEC. CARDIAC RATE AND C.O
 RELAXATION OF CAPACITANCE
VESSELS---DEC IN PVR

TOXICITY
 SEDATION
 DRY MOUTH
 MENTAL DEPRESSION----WITHDRAW
 WITHDRAWAL AFTER PROTRACTED
USE:
LIFE THREATENING HYPOTENSIVE
CRISIS
 Nervousness, tachycardia, headache &
sweating---omitting 1 or 2 doses of drug

DRUG INTERACTIONS
 TCA MAY BLOCK THE ANTI
HYPOTENSIVE EFFECT
 NSAIDS MAY ENHANCE THE
ANTIPOTENSIVE EFFECT

OTHERS..
GUANABENZ
GUANFACINE
RARELY USED….

GANGLION BLOCKING
AGENTS
 MOA
 COMPETITIVELY BLOCK NICOTINIC
CHOLINOCEPTORS ON POST
GANGLIONIC NEURONS IN
BOTH SYMPATHETIC &
PARASYMPATHETIC OUTFLOW
 MAY DIRECTLY BLOCK
NICOTINIC Ach channel

TO NAME A FEW..
HEXAMETHONIUM
MECAMYALINE
TRIMETHAPHAN

ADVERSE EFFECTS
 SYMPATHOPLEGIA: excessive
orthostatic hypotension & sexual
dysfunction
 PARASYMPATHOPLEGIA:
constipation, blurred
vision, precipitation of glaucoma, dry
mouth, urinary retention

ADRENERGIC NEURON
BLOCKING AGENTS
 MOA
PREVENT NORMAL PHYSIOLOGICAL
RELEASE OF NOREPINEPHRINE
FROM POST GANGLIONIC
SYMPATHETIC NEURONS

GUANITHIDINE
 MOA---transported across symp nerve
ending by NET, conc. In vesicles, NE
replaced….gradual depletion of NE

TOXICITY
 SYMPTOMATIC POSTURAL
HYPOTENTION OR AFTER EXERCISE
 DIARREHA
 DELAYED OR RETROGRADE
EJACULATION

CONTRA-INDICATIONS
 SYMPATHOMIMETIC AGENTS—cause
HYPERTENSION
 CAN PRODUCE HYPERTENSIVE
CRISIS BY RELEASING
CHATECHOLAMINES IN PTS WITH
PHEOCHROMOCYTOMA
 TCA ATTENUATE
ANTIHYPERTENSIVE EFFECT---
SEVERE HYPERTENSION

THESE BLOCK NEURONAL
UPTAKE OR DISPLACE
AMINES FROM NERVE
TERMINALS
 COCAINE
 AMPHETAMINE
 TCA
 PHENOTHIAZINES
 PHENOXYBENZAMINE

RESERPINE
 MOA
 Blocks the ability of aminergic
transmitter vesicles to take up and store
biological amines----interfere VMAT
 -> DEPLETION OF
NE, DOPAMINE & SEROTININ
BOTH IN CENTRAL AND PERIPHERAL
NERVOUS SYSTEM
 CROMAFFIN GRANULES OF AD.
MEDULLA ARE ALSO DEPLETED

TOXICITY
 LOW DOSES—LITTLE POSTURAL
HYPOTENSION
 HIGH DOSES–
SEDATION, LASSITUDE, NIGHTMARE
S, SEVERE MENTAL DEPRESSION—
occasionally with low doses too
 EXTRAPYRAMIDAL EFFECTS due to low
dopamine in CS.
 GIT MILD DIARREHA, GIT
CRAMPS, INCREASED GASTRIC ACID
SECRETION
 CONTRAINDICATED WITH H/O
PEPTIC ULCER

PROPRANOLOL
 MOA
 NONSELECTIVE β- BLOCKADE
 PRIMARILY DECREASE IN CARDIAC OUTPUT
 INHIBITS STIMULATION OF RENIN
PRODUCTION BY
CATECHOLAMINES( β1)
 ACTS ON PERIPHERAL PRESYNAPTIC β-
ADRENOCEPTORS TO REDUCE
SYMPATHETIC VASOCONSTRICTIVE
ACTIVITY
 IN MILD TO MODERATE HYPERTENSION
SIGNIFICANT REDUCTION IB B.P WITHOUT
PROMINENT POSTURAL HYPOTENSION

TOXICITY
 BRADYCHARDIA
 WORSONED ASTHAMA
 FATIGUE
 VIVID DREAMS
 COLD HANDS
 DISCONTINUATION AFTER
PROLONGED REGULAR USE
WITHDRAWAL SYNDROME:
nervousness, tachycardia, increased
intensity of angina, increased B.P

OTHERS
 METOPROLOL & ATENOLOL
 GREATER SELECTIVITY TO β1-
ADRENOCEPTERS
 INDICATIONS:
HYPERTENSION, ARRYTHMIAS, ANGIN
A, EARLY MANAGEMENT OF MI
 Metoprolol thyrotoxicosis &
migraine prophylaxis

 NADOLOL & CARTEOLOL:
NONSELECTIVE β - RECPTOR
ANTAGONISTS, REDUCED
DOSES IN RENAL DISEASE
 BETAXOLOL &
BISOPROLOL:β1 BLOCKER

PINDOLOL, ACEBUTOLOL, P
ENBUTOLOL
 PARTIAL AGONISTS: β- BLOCKERS
WITH SOME INTRINSIC
SYMPATHOMIMETIC ACTIVITY
 REDUCE VASCULAR
RESISTANCE
 REDUCE CARDIAC OUTPUT OR
H.R LESS THAN OTHERS due to
agonist activity beneficial in cases of
bradyarrhythmias or PVD

LABETOLO, CARVEDILOL, NE
BIVOLOL
 β- BLOCKING AND VASODILATING
ACTIVITY
 LABETOLOL: 4 ISOMERS; 3:1 RATIO
OF β:α BLOCKADE
REDUCED SYSTEMIC VASCULAR
RESISTANCE(α-
BLOCKADE), COMBINED ACTIVITY
PHEOCROMOCYTOMA &
HYPERTENSIVE EMERGENCIES

CONT..
 CARVEDILOL: HEART FAILURE
AND HYPERTENSION
 NEBIVOLOL:
 D- ISOMER: β-1 SELECTIVE
 L-ISOMER: NITRIC OXIDE
SYNTHASE INDUCER PVR is
acutely lowered, has fewer side effects

ESMOLOL
 β1- SELECTIVE BLOCKER
 RAPIDLY METABOLISED BY RBC
ESTERASES
 INDICATIONS: INTRA & POST
OP
HYPERTENSION, HYPERTENSIV
E EMERGENCIES PARTICULARLY
WHEN HYPERTENSION IS ASSOCATED
WITH TACHYCARDIA

PRAZOSIN & OTHER α1
BLOCKERS
 SELECTIVE BLOCKAGE OF α1
RECEPTORS IN ARTERIOLES &
VENULES
 LESS REFLEX TACHYCARDIA THAN
WITH NON SELECTIVE α BLOCKERS EG
PHENTOLAMINE
 DLATION OF RESISTANCE &
CAPACITANCE VESSELS
 B.P more in UPRIGHT position
 More effective with β blockers & a diuretic

TAMSULOSIN
INDICATED IN
BENIGN PROSTATIC
HYPERPLASIA &
HYPERTENSION

TOXICITY
 FIRST DOSE SYNCOPE:
PRECIPITOUS DROP IN STANDING B.P
AFTER 1ST DOSE 1ST DOSE
ADMINISTERRED AT BEDTIME; Occurs in
salt & vol. depleted pts
 DIZZINESS
 PALPITATIONS
 LASSITUDE
 HEADACHE
 +VE TEST FOR ANTI NUCLEAR
FACTOR BUT NO ASSOC. WITH R.A

NONSELECTIVE α BLOCKERS
 PHENTOLAMINE
+PROPRANOLOLCLONIDINE
WITHDRAWAL SYNDROME
 PHENTOLAMINE &
PHENOXYBENZAMINE:
PHEOCHROMOCYTOMA

VASODILATORS
ORAL
PARENTRAL
Ca BLOCKERS

HYDRALIZINE
 RELEASE OF N2O
 ARTERIOLAR DILATION
 TACHYPHYLAXIS TO ANTI-HTN
EFFECTS DEVELOPED RAPIDLY
 Low bioavailability ; first pass
metabolism by acetylation

TOXICITY
 Headache
 Nausea
 Palpitation
 Sweating
 Flushing
 Anorexia
 May provoke ANGINA or ISCHEMIC
ARRHYTHMIAS
 LUPUS-LIKE SYNDROME
arthralgia, myalgia, skin rashes, fever
 Peripheral neuropathy and drug
fever…RARE

MINOXIDIL
 SULPHATE DERIVATIVE OPENS
POTASSIUM CHANNELS IN SMOOTH
MUSCLESHYPERPOLARIZATION
ARTIRIOLAR DILATION
 INDICATIONS: HTN, HEART
FAILURE, BALDNESS(local action)

TOXICITY
 TACHYCARDIA, PALPITATIONS, ANG
INA, EDEMA WITHOUT β-
BLOCKER & DIURETIC
 HEADACHE, SWEATING, HYPERTRIC
HOSIS…RELATIVELY COMMON

SODIUM NITROPRUSSIDE
 INDICATIONS; HYPERTENSIVE
EMERGENCIES & HEART FAILURE
 MOA: ACTIVATION OF GUANYLYL
CYCLASE( VIA N2O OR DIRECT) INC.
INTRA CELLULAR cGMP RELAXES
VASCULAR SMOOTH MUSCLE
ARTERIAL & VENODILATION
 In pts with heart failure & low cardiac
output..output inc owing to afterload
reduction

DIAZOXIDE
 EFFECTIVE & LONG ACTING
 ARTERIOLAR DIATOR
 RAPID FALL IN SYSTEMIC
VASCULAR RESISTANCE
 OPENING OF POTASSIUM
CHANNELS
 HYPOTENSION ACHIEVED WITH
SMALLER DOSES IN CHRONIC
RENAL FAILURE
 Hypoglycemia secondary to
insulinoma

TOXICITY
CAN PROVOKE
 ANGINA
 ECG EVIDENCE OF ISCHEMIA
 CARDIAC FAILURE,
In pts with ischemic heart disease
 HYPERGLYCEMIA , particularly in pts
with RENAL INSUFFISIENCY

FENDOLOPAM
 PERIPHERAL ARTERIOLAR DILATOR
 HYPERTENSIVE EMERGENCIES &
POST-OPERATIVE HYPERTENSION
 AGONIST OF D1 RECEPTORS:
PERIPHERAL ARTERIAL DILATION &
NATRIURESIS.
 Metabolized by conjugation

TOXICITY
 REFLEX TACHYCARDIA
 HEADACHE
 FLUSHING
 INCREASES INTRAOCULAR
PRESSURE…CONTRAINDIC
ATED IN GLAUCOMA

Anti Hypertensives- pharmacology

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