ANTI-HYPERTENSIVE MEDICATION

1. ANTI-HYPERTENSIVE
MEDICATIONS
PRESENTATION BY:
MOHAMMED MAQSOOD
PHARM.D VI YEAR

2. CONTENTS
1. Who are the candidate for treatment?
2. Health behavior management
3. Which non drug measure is effective in
reducing blood pressure
4. Anti-hypertensive drugs
5. Strategies to dose antihypertensive drugs

3. Who are the candidate for treatment?
Population HTN JNC 8 2014 TARGET
General > 60 year Consider Tx if >
150/90mmHg
<150/90 mmHg
General < 60 year Consider Tx if SBP > 140
mmHg or DBP > 90mmHg
<140/90mmHg
DM Consider Tx if >140/90
mmHg
<140/90 mmHg
CKD Consider Tx if >140/90
mmHg
<140/90 mmHg

4. Health behavior management

5. Which non-drug measure is effective in reducing
blood pressure?
Systolic: DASH > exercise > weight
loss > low Na > low alcohol
Diastolic: Exercise > weight loss >
DASH > low Na > low alcohol

8. Mechanism of action of diuretic

9. Chlorothiazide HydroChlorothiazide
Chlorthalidone Indapamide
THIAZIDE DIURETICS

10. Thiazide Diuretics
THIAZIDE
DIURETICS
Notes
INDICATIONS Uncomplicated HTN, ISH, Diastolic HTN, DM without
albuminuria, non-DM CKD, Edema, prevention of
renal calculi(↑ Ca+2), Diabetes insipidus, Preeclampsia
in pregnancy, TIA/stroke(+ ACE), Ascites (CL hepatic
coma)
Hypovolemia-loop prefered Non-
DM CKD- No indapamide
Contraindications Hypersensitivity(sulfa allergy)
THD & LD(except ethacrynic acid)
Anuria (ARF, hemolysis)
Hepatic coma
Cross sensitivity is rare
metolazone- unlikely (monitor for 6
months)
Avoid sun exposure
Mannitol
Encephalopathy

11. Notes
ADR Hypokalemia
hyponatremai, hypochloremia
Hypomagnesemia, Hypercalcemia(interfere
with parathyroid test)
Risk ↑ in elderly and patients with renal
impairment/HF
Potassium rich food (banana, almonds)
Vitamin D ↑ hypercalcemia
Topiramate, corticosteroids ↑ hypokalemia
DM- dose dependant
Hyperlipidemia- ↑ LDL, TC, TG
Gout (↑ uric acid level)
(hypokalemia-↓ insulin secretion and ↑
insulin resistance)
Tetracycline ↑ uric acid level
Arrythmia (electrolyte abnormalities)
orthostatic hypotension
↑ with alcohol/opioids/barbiturates/ anti-
HTN
Drug interactions ↑ lithium toxixity ↓ Li dose by 50% / monitor serum conc?
electrolytes?
↑ Digoxin toxicity (Diuretic induced
hypokalemia)
Monitor electrolyte?
K+ sparing diuretic
↑ risk of allopurinol induced hypersensitivity
effect
NSAIDS, Quinidine, Alcohol, Barbiturates,
Opioids, Cholestyramine

12. Pharmacokinetic
 They are well absorbed on oral administration.
 Onset of action is quick, while duration of action is dependent on their lipid
solubility. high lipid soluble drugs are longer acting due to greater volume of
distribution, greater protein binding, greater tubular reabsorption.
 They are secreted into the tubules by organic acid transport and are excreted
unchanged in urine.
 Hepatic metabolism is less but indapamide is primarily excreted by biliary
system.
Drug Bioavailability Plasma half life Duration of
action
Hydrochlorothiazide 70% 2.5 hrs 12 hrs
Chlorthalidone 65% 24 hrs 24-48 hrs
Indapamide >90% 18 hrs 24 hrs

13. Key notes!!!!
 Monitor Scr ( caution in Crcl < 45 ml/min,
metolazone and loop are prefered in the
popualtion)
 Monitor BUN, Electrolytes, BG and lipids
 LFT, AST, ALT ????
 Take with or without food
 Be careful if using contact lenses (dry eye)
 Avoid sun exposure
 Avoid the diuretic after 4 PM
 Conflicating data regarding safety on pregnancy
and breast feeding

14. Loop diuretics
Indications:
 Edema
 Oliguria
 Treatment of hypercalcemia
 Mild- moderate HTN ( in patient with HF or CKD) not 1st line
Key notes:
 More potent
 ↑ BG, uric acid level
 ↓ K+ / Na +/ hypovolemia / Ca 2+ (do not restrict salt intake)
 D/C prior to surgery (IV- 2 DAYS/ po-1 week) ↑ effect of NMJ blocking agent
 Avoid doses after 4 PM
 Ototoxicity

15. Spironolactone
Indications:
Primary aldosteronism, HF, Edema/ascites in lower cirrhosis, hypokalemia
Contraindications:
Hypersensitivity, anuria, hyperkalemia, renal impairment, UFH & LMWH
ADR
Hyperkalemia, hyponatremia, gynecomastia, leg cramps, rash
Monitor
SCr and K+ 3 days and 1 week after initiating therapy. D/C if K+ >5mmol/L

16. Angiotensin converting enzyme inhibitors(ACEI)

17. Angiotensin converting enzyme inhibitors(ACEI)
• 1st line for HF
• HTN + LVH/ MI/ DM/ CKD
• Post MI
• Less effective in african -american ( note: HF/CKD/MI)
Indications:
Contraindications:
Hypersensitivity
Hx of angioedema by ACE
Pregnancy2nd and 3rd trimester- fetal renal failure and IUGR
Concern pr-contrast coronary angiography
Structure of Captopril

18. Adverse reactions:
 Angioedema (prevalent in african american) / Quincke’s edema
 Rash
 Hypotension
 Cough (dry, non-productive/ prevalent in east asian, non-smokers, female, HF)
 Hyperkalemia (D/C if K+ >5.6 mmol/L)
 Impaired renal function
 Hepatotoxicity
 Neutropenia / agranulocytosis
 Dysgeusia
 Photosensitivity?
 Excessive dose cause reversible tachycardia, hypotension, vascular collapse
Pharmacokinetics: It is well absorbed on oral administration. Food delay the absorption
of captopril, but not other drugs. so, it should be taken before meal. Captopril has faster
onset of action but less duration of action compared to enalapril, lisinopril. It is
metabolised in liver and excreted in urine.

20. Drug interactions:
• Allopurinol
• Drugs that ↑ K+
• lithium
• THD, alpha 1 blockers
• Insulin and anti-DM agents
• DDP-4
• TCAD, Antipsychotics
Monitoring:
• Monitor 1-2 weeks after intiation or dose increase than annually
• K+ level ( D/C if > 5.6 mmol/L)
• Scr ↑ > 30% of the baseline ( D/C ACEI)

22. Angiotensin II receptor blockers
Indications
• 1st line in uncomplicated HTN
• HTN + DM, LVH, ISH
• Alternate to ACEI
Structure of losartan
Pharmacokinetics:
 Oral bioavailability is low(33%) and food does not
interfere with absorption except valsartan.
 It is partially carboxylated in liver to an acive
metabolite(except telimisartan) which is 10-30 times
more potent AT1 receptor antagonist.
 It is highly bound to plasma proteins and excreted in
urine.
 Its action lasts for 24 hrs.

23. Angiotensin II receptor blockers
Drug t1/2 Elimination Daily dose
mg/day
Frequency
Losartan 2 hrs Hepatic and
renal
25-100 OD-BD
Candesartan 8-12 hrs Hepatic and
renal
8-32 OD-BD
Valsartan 6-9 hrs Mainly hepatic 80-320 OD
Telmisartan Hepatic 20-80 OD
Irbesartan 12 hrs Mainly hepatic 75-300 OD

24. Aliskerin
Indications
HTN+/- Diuretic and DHPCCB
Contraindication
Pregnancy, lactation, Hx of angioedema, +ACE/ARBS
Adverse drug reactions
↑K+, angioedema, cough (rare), nasopharyngitis, headache, diarrhea, rash, gout
Drug interaction
Avoid use with cyclosporine, azoles antifungals,and grapefruit juice

25. Beta Blockers
Cardioselective
Esmolol
Metaprolol
Acebutalol
Atenolol
Bisoprolol
Nebivolol
Non-selective
Propranolol
pindolol
Nadolol
Tionaletimo
lol
Sotalol
Vasodilator
betablocker
Carvedolol
Labetalol
Betablocker
with ISA
Acebutalol
Pindolol
Oxeprenol
ol

27. α+β Adrenergic blockers
Labetalol: It is capable of blocking beta receptors (β1, β2) than
alpha receptor (α1). It is 5 times more potent in blocking β receptors
than α receptors.
Indication: i. Prefer anti-hypertensive for rise in BP due to preclampsia
ii. oral therapy in moderately severe HTN not responding to
β blocker
iii. IV for rapid reduction in hyperadrenergic state.
Adverse effects: Postural hypotension, rashes and liver damage
Drug interaction: cimetidinr, digitalis, guanethidine
Contraindiation: CHF, heart failure, asthma, severe bradycardia, prolonged hypotension
Pharmacokinetics: Orally absorbed completely in GIT with bioavailability of 90-100%.
Plasma half life is 6-8 hours. Metabolism is primarily due to conjugation to glucuronide
metabolites. Elimination is occur in urine
Dose: 300-600mg/day
Carvedilol: It is a non selective β blocker and weak selective α1 blocker which produce
vasodilatation and has anti-oxidant/ free radical scavenging properties
Indication: HTN and long term treatment of CHF

28. α Adrenergic blocker
Prazosin:
Mechanism of action: It act by blocking α1 adrenergic receptor of vascular smooth muscle, this
decrease in the level of intracellular Ca+2 and relax arterial and venous smooth muscle leading to
vasodilation.
Indication: Moderately potent anti-hypertensive, but not used as first line drug because of fluid
retention and tolerance gradually develop with monotherapy.It is used in combination with diuretic
with β blocker those not achieving target BP.
Caution: Postural hypotension and fainting may occur in the beginning called ‘first dose effect’,
and with dose increments. This disappears with continued therapy, but may persist in the elderly.
For this reason, prazosin is always started at low dose (0.5 mg) given at bedtime and gradually
increased with twice daily administration till an adequate response is produced (max. dose 10 mg
BD).
ADR: Headache, drowsiness, dry mouth, weakness, palpitation, nasal blockade, blurred vision
and rash. Ejaculation may be impaired in males.
Pharmcokinetics: It is well absorbed orally and is mainly metabolised in liver. The metabolites
are responsible for hypotensive action. plasma half life is 120-180 min which increase by 2 fold in
case of CHF.The unchanged drug is eliminated through kidney
Other drugs like terazosin and doxazosin are long acting congeners of prazosin with similar
properties but suitable for one daily dosing.

29. Central sympatholytics
Clonidine:
Mechanism of action: It act by stimulating α2A adrenergic
receptors in the vasomotor center in the medulla thereby
reducing sympathetic outflow and noradrenaline release leading
to decrease in BP and bradycardia.
Indication: In HTN, occasionally used in combination with diuretics.
Pharmacokinetics: Clonidine is well absorbed orally; peak occurs in 2–4 hours; 1/2 to 2/3 of
an oral dose is excreted unchanged in urine, the rest as metabolites. Plasma t½ is 8–12
hours. Effect of a single dose lasts for 6–24 hours.
Dose: Start with 100 μg OD or BD, max. 300 μg TDS, orally or IM
ADR: Common effects are sedation, dry mouth and costipation. Impotence, salt and water
retention, bradycardia (due to reduced sympathetic tone). Postural hypotension occurs, but is
mostly asymptomatic.
Rebound hypertension occurs following abrupt withdrawal of clonidine. The drug should
therefore be withdrawal slowly if discontinuation is required.
Druh interactions: Tricyclic antidepressants and chlorpromazine abolish the antihypertensive
action of clonidine, probably by blocking α receptors on which clonidine acts

30. Central sympatholytics
Methyldopa:
Mechanism of action: It is a prodrug which is converted to
α methyl noradrenaline in the adrenergic neurons. The
α methyl noradrenaline acts on the central α2 receptors
in the vasomotor center of medulla, to reduce the sympathetic activity and noradrenaline release leading to
decrease in BP.
Indication: Methyldopa is a moderate efficacy antihypertensive and rarely used now to treat hypertension
during pregnancy wherein it has a long track record of safety, both for the mother as well as the foetus.
Pharmacokinetics: Though methyldopa is transported to brain actively by intestinal amino acid carrier, less
than 1/3 of an oral dose is absorbed. It is partly metabolized and partly excreted unchanged in urine.
Antihypertensive effect develops over 4–6 hours and lasts for 12–24 hours.
Dose: 0.25–0.5 g BD–QID oral
ADR: Sedation, lethargy and reduced mental .capacity are common side effects. Postural hypotension are
mild but more common than with clonidine;
Rebound hypertension on sudden withdrawal of methyldopa is mild and less common.
Drug Interactions: Tricyclic antidepressants reverse its action by blocking its active transport into the
adrenergic neurones.

31. Calcium channel blockers
1. Dihydropyridine (DHP) : Properties is similar to peripheral vasodilators.
2. Non-dihydropyridine (Non DHP) : Properties is similar to β blocker and not combined with β blocker.
Indication:
HTN > 55 years, Non DHP is recommend in atrial fibrillation and atrial flutter, DHP is
recommend in angina/prinzmetal and migraine prevention (flunarizine)
Contraindication:
Non DHP same as β blocker, severe aortic stenosis (DHP worsen DBP)
Adverse drug reaction
CVS: Peripheral/facial/pedal edema, bradycardia(Non DHP), tachycardia(DHP)
CNS: Headche, fatique, dizziness, depression (flunarizine)
GIT: Gingival hyperplasia (20% with nifedipine), constipation (worst with verapamil)

32. Arteriolar Vasodilators
Hydralazine:
Mechanism of action: It cause direct relaxation of blood veesels by activating K+ channels thereby
reducing peripheral vascular resistance with a consequent fall in BP. The other mechanism of
vasodilation include generation of nitric oxide.
Indication: It is rarely used as 2nd line alternative only in combination with diuretic and β blocker for
patients not achieving target BP with first line agents. Injected hydralazine is occasionally employed in
hypertensive emergencies.
Contraindication: Older patients and in those with ischaemic heart disease.
Pharmacokinetics: It is well absorbed from GIT on oral adminstration. It is metabolized in liver by
acetylation. The plasma half life of the drug is 1-2 hrs. but antihypertensive effect is long(12hrs) because
of persistence in the vessel wall.
Dose: 25-50 mg OD-TDS
ADR: Facial flushing, throbbing headache, dizziness, palpitation, nasal stuffiness, edema, CHF.
Lupus erythematosus or rheumatoid arthritis like symptoms develop on prolonged use of doses above
100 mg/day. It is more common in women and in slow acetylators.
Minoxidil: It is a powerful vasodilator, the pattern of action resembling hydralazine. Risk of caridac
ischemia and heart failure is high, it is not used orally. Hirsutism was observed as side effect of
minoxidil.

36. How to improve patient medication adherence?
• Combination pills
• Monthly remainder
• Educate patient
• Put pills in a divided section in a box
• Ensure affordability (by recommending generic
drug)
• Dosage simplication