ANTIHYPERTENSIVES 1.0 Flashcards
Give the classification of antihypertensive drugs
Diuretics
Sympatholytic drugs
Calcium channel blockers
Drugs acting on RAAS
Vasodilators
Give the Sympatholytic agents for hypertension
1) Alpha receptor antagonists
2) Beta receptor antagonists
3) Mixed beta and alpha receptor antagonists
4) Centrally acting adrenergic receptor agents
5) Adrenergic neuron blocking agents
Give the centrally acting receptor agonists
Methyldopa
Clonidine
Guanabenz
Guanfacine
Give the mechanism of action of the centrally acting antihypertensive agents
They act on a2 receptors in the brainstem for sympathetic inhibition by inhibiting release of NE
What is the function of the a2 receptors
When stimulated they inhibit NE release through feedback mechanism
What type of G protein coupled receptor is a2 receptor
Gi
Methyldopa is termed as a prodrug , explain
Methyldopa is converted to its active form methylnorepinephrine that works to stimulate the a2 receptors in the brainstem thus inhibiting NE release
Give five PK of methyldopa
1) Taken orally
2) Rapidly absorbed
3) Metabolized in the brain
4) Half life of two hours
5) Excreted in urine as sulfate conjugate(50-70%) and parent drug (25%)
Give uses of Methyldopa
Used as a hypertensive drug in pregnancy
Give the A/E of methyldopa
Dry mouth , Sedation , Hemolytic anemia (discontinue) , Positive Coombs test , Thrombocytopenia , Leukopenia , Red cell Aplasia , Prolactinemia , Parkinsonism
Clonidine is said to have two a2 receptor effects , give them
A2a stimulation in brainstem to reduce NE release
A2b stimulation in bloodvessels to bring vasoconstriction (high doses)
Clonidine reduces blood pressure by reducing the CO and PVR ,Explain
BP = CO X PVR
Clonidine reduces the CO in supine by
Reducing the HR , Stroke volume and myocardial contractility
It reduces the PVR in postural position
Reduction in the Myocardial contractility of Clonidine can predispose a patient to
Congestive Heart failure
Give atleast 10 A/E of Clonidine
sedation , dry mouth, nose and eyes , Erectile dysfunction , vivid dreams , depression , restlessness , sinus arrest , postural hypotension
To treat the withdrawl that comes fro sudden discontinuation , three things can be done?
1) Restore the drugs
2) Give sodium nitroprusside
3) Hive mixed alpha and beta blockers
Sudden discontinuation of Clonidine can lead to withdrawl effects such as
Headaches , Tremors , Apprehension , Abdominal pain , Tachycardia , Rebound hypertension
Clonidine is rarely used for hypertension. Give an important use of Clonidine.
Diagnosis of Phaeochromocytoma
Give two main Adrenergic blocking agents
Reserpine and Guanethidine
Give the mechanism of action of Guanethidine
Transported into the presynaptic membrane by NET transporters and stored in the NE vesicles thus deplets NE stores
Give the mechanism of action of Guanethidine
Transported into the presynaptic membrane by NET transporters and stored in the NE vesicles thus deplets NE stores
NET is inhibited by
Cocaine , Amphetamine, Tricyclic antidepressants , Phenoxybenzamine
Give the PK of Guanethidine
Has a long half life of 5 days
Gradual onset of sympathoplegia with maximal effect in 2 weeks
Persisiting sympathoplegia even after cessation
Titrate dose of drug in 2week interval
Give four A/E of Guanethidine
1) Postural hypotension
2) Retrograde ejaculation
3) Diarrhea
4) Hypertensive crisis in pheochromocytoma
Give two main DDI in Guanethidine
Sympathomimetic agents - worsen hypertension
Tricyclic antidepressants
Give the MOA of reserpine
Irreversibly Blocks the vessicle associated membrane transporter thus depletion of NE, serotonin and dopamine stores
Give A/E of Reserpine
Severe depression ( discontinue)
Sedation
Nightmares
Parkinsonism
Postural hypotension
GIT problems
Alpha receptor antagonists may be grouped into 3
1) Non selective
2) Selective
3) Ergot alkaloids
Give the non-selective alpha receptor antagonists.
PPUTY
Phenoxybenzamine
Phentolamine
Urapidil
Tolazoline
Yohimbine
Give the non-selective alpha receptor antagonists preferrentials
Phenoxybenzamine - a1 more than a2
Phentolamine - a1=a2
Urapidil - a1 more than a2
Tolazoline and Yohimbine - a2 more than a1
Give the selective alpha receptor antagonists
PTTD
Prazosin , Terazosin , Trimazosin , Doxasozin
TA
Tamsulosin and Alfuzosin
Give the types of beta receptor antagonists
1) Non-selective
2) Selective
3) Combined
Give the none selective beta blockers
Propranolol
Pindolol
Timolol
Give examples of selective beta blockers
b1 - Metoprolol, Betaxolol ,bisprolol ,atenolol, acebutolol, Tolamolol
b2 - butoxamine
Give the mixed alpha and beta receptor antagonists
Labetolol
Carvedilol
Give the MOA of Phenoxybenzamine
Irreversibly blocks alpha adrenoreceptors and thus reduce vasoconstriction cause by norepinehrine and epinenphrine
What is the main clinical use of phenoxybenzamine
Pre and intra operative management of pheochromocytoma
Give the A/E of phenoxybenzamine
Postural hypotension
Dry mouth
Inhibiton of ejaculation
Nasal stuffiness
Miosis
Give three absolute C/I of Phenoxybenzamine
Porphyria
Hypovolemic states
History of cerebrovascular accidents
Give relative C/I of phenoxybenzamine
Elderly patients
Pregnancy
Renal imparement
Marked arterioscleorsis
ACE inhibitors have 2 main types of moa
1) Prevent conversion of Angiotensin I to II which is a potent vasocntrictor
2) Inhibits breakdown of bradykinin thus causes its accumulation and an increase in nitric oxide and prostacyclin which are potent vasodilator
ACE inhibitors have 2 main types of moa
1) Prevent conversion of Angiotensin I to II which is a potent vasocntrictor
2) Inhibits breakdown of bradykinin thus causes its accumulation and an increase in nitric oxide and prostacyclin which are potent vasodilator
ACE inhibitors are used in which type of hypertensive pateints
Patients with co morbidities such as diabetes ,
All ACE inhibitors are guven orally except
Enalaprilat
All ACE inhibitors are eliminated by the kidneys except
Fosinopril
All ACEIs undego hepatic metabolism to active metabolites except
Captopril and Lisinopril
ACEIs adverse effects include
Dry cough , rash , fever , altered taste , hypotension and hyperkalemia
What rare but life threatening A/E may be associated with ACEIs
Angioedemea
Which two things must be monitored in patients using ACE inhibitors
1) Potassium
2) Serum creatinie
Give two examples of ARBs
Losartan and irbersartan
ARBs are similar to ACE inhibitors but differ in one of the mechanisms
ARBs do not increase bradykinin levels
Give a C/I for ACE inhibitors and ARBs
Pregnancy - teratogenic
Give the three main classes of drug sas RAAS modulators and examples
1) ACE inhibitors - Lisinopril , Etanapril
2) ARBs - Losartan ,
3) Direct Renin inhibitors - Aliskerin
