Antihypertensive Drugs

Question 1

BP Equation

Answer 1

BP= CO x peripheral vascular resistance

Question 2

Drug Categories

Answer 2

Diuretics
Sympathoplegic Drugs
Direct Acting Vasodilators
Inhibition of RAAS

Question 3

Diuretics used for Hypertensive th

Mech of Action

Answer 3

Decrease circulating volume and therefore –> resistance
Acute: Reduce blood volume and CO, after a few weeks CO normalises

Depletion of Na stores–> Na/Ca exchanger accelerated-> less IC Ca–> decrease tone

Lower BP by 10-15mmHg

In Combo with beta blockers, ACE inhibitors, angiotensin 2 antagonist

Question 4

Diuretics used for Hypertensive th

Chronic th: Drugs

Answer 4

Thiazide
Hydrochlorothiazide
Clopamide

K sparing
Amiloride
Triamterene
Spirolactone

Example for a combo:
Amiloride + Hydrochlorothiazide

Question 5

Diuretics used for Hypertensive th

Acute th: Drugs

Answer 5

Loop Diuretics (IV)

Furosemide

Question 6

Direct Acting Vasodilators (decrease resistance and increase capacitance)

Ca Channel Blockers

Answer 6

DHP only (non DHP cause reflex tachycardia)
   Nitrendipine
   Nifedipine
   Nimodipine
   Amlodipine
   Felodipine

Question 7

Direct Acting Vasodilators

K Channel Activator

Answer 7

Minoxidil (prodrug)
Active: Minoxidil sulphate

Activated ATP mediated K channel–> hyperpolarisation of SM–> relaxation

Side Effects:
Fluid and Na retention
CV (baroreflex, increased CO)
Hair growth

Diazoxide
Only IV and for severe, emergency th (effect within 3 min)

Question 8

Direct Acting Vasodilators

Agents that increase cyclic nucleotide conc

Answer 8

Na Nitroprusside
Complex: Iron + cyanide + Nitroso moiety–> rapidly metabolised to release cyanide (toxic for those with cyanide metabolism defect)

Na Nitroprusside and Nitrates such as Nitroglycerine
Activation of gualylyl cyclase (release of NO or direct enzyme stimulation)–> increased IC cGMP-> relaxation

Sensitive to light–> brown glass container

Question 9

Direct Acting Vasodilators

Vasodilators with unknown mech of action

Answer 9

Hydralazine (rarely used)

Side Effects:
   headache
   nausea
   drug induced SLE
   vasculitis

Question 10

Inhibition of RAAS

Answer 10

Decrease resistance, decrease circulating volume, decrease arterial remodeling

Renin release inhibitors: Beta 1 Blockers
Atenolol, Bisoprolol, Esmolol, Metoprolol

Renin Activity Inhibitors: Aliskiren

ACE Inhibitors
Captopril, Ramipril, Enalapril, Lisinopril, Benzapril, Ramipril, Fosinopril

AT1 R Antagonist
Losartan, Valsartan, Irbesartan, Candesartan

Question 11

Location of AT1 R Predominantly

Answer 11

Vascular tissue
Brain
Myocardial tissue
Kidney
Adrenal Gland

Question 12

Centrally Acting Sympathoplegic Drugs

Answer 12

Sympathoplegic: Altering the symp NS function

Methyldopa (prodrug, mother compound)
Similar to DOPA in chemical structure
Can enter brain as prodrug
Competitive inhibitor of NE production: false substrate–
> converted into alpha methyl NA (active metabolite) =
a2 R agonist–> negative feedback

Reduces tone of vasomotor center in CNS
Anti Hypertensive effect via diminishing vasomotor
center activity

Peripheral effect not responsible for antihypertensive
effects

Safe to use during pregnancy

Side effects: Sedation, depression, impaired mental
concentration, vertigo

Clonidine, Guanfacine, Guanabenz (Imidazole deriv)
Also bind to non adrenergic binding site of presyn
membrane (Imidazoline R)–> inhibition of NA release
Alpha Methyl NA can’t bind to imidazoline R
Side Effects: similar to alpha methyldopa

Moxonidine
New Imidazole derivative; binds only to imidazole R

Question 13

Ganglion Blocking Agents//
Presynaptic sympath. R blockers

Mode of Action

Answer 13

Intolerable toxicities–> most not used anymore

Competitive antagonists on nicotinic R–> non depolarising ggl blocker

Problem: Block sympath. and parasymp ggl

Question 14

Ganglion Blocking Agents//
Presynaptic sympath. R blockers

Drug Name

Answer 14

Trimethaphan
Side Effects: orthostatic hypotension, sexual dysfunction
constipation, urinary retention, glaucoma, dry mouth

Question 15

Adrenergic Neuron Blocking Agents

Answer 15

Guanethidine: Not used due to side effects
Inhibits AP induced exocytic NA release
Doesn’t enter CNS–> effects only in periphery

1) Indirect sympathomimetic effect (tyramine like effect)
2) Concentrated in transmitter vesicle, replacing NA–
>MAO depletes NA–> reserpine like effect

Side Effects: postural hypotension, sympathoplegia,
diarrhea (parasymp. predominance)

Reserpine: not really in use due to side effects
(depression)
Inhibition of vesicular NA + dopamine transport
Irreversible inhibitor of VMAT1 + 2

Question 16

Adrenergic R Antagonists

Selective Alpha 1 Blocker

Answer 16

Decrease vascular resistance

Prazosin, Doxazosin, Terazosin
Last two have longer T1/2

Side Effects: postural hypotension, reflex tachycardia

Question 17

Adrenergic R Antagonists

Selective Beta 1 Blocker

Answer 17

Metoprolol (mother compound)
Atenolol
Bisoprolol
Nebivolol
Celiprolol

Decrease CO

Question 18

Adrenergic R Antagonists

Alpha and Beta Blocker

Answer 18

Labetolol

Used for: pheochromocytoma
Hypertensive crisis