hypertensive drugs in various conditions.pptx

Electrolyte imbalance
Metabolic: hyperglycemia, hyperlipidemia, hyperuricemia.
Erectile dysfunction
Not effective in chronic renal disease.
More effective in elderly: also in patients with isolated systolic hypertension.
Long acting, used once a day
No tolerance and no fluid retention
Reduce calcium excretion, preferred in osteoporosis (especially older women).
Hydrochlorothiazide is one commonly used thiazide and consider as 1st choice.
the main problem with thiazide is hypokalemia and this can be avoided by K+ supplementation or using K+ sparing diuretics.
However, ACEI/ARBs should not combined with K+ sparing diuretics which cause dangerous hyperkaliemia in some pt.
Indications: HT, especially co-existing with:-
DM,
Nephropathy,
Left Ventricular Hypertrophy (LVF),
Chronic Heart Failure (CHF),
Angina,
Post Myocardial Infarction (MI) cases.
ADRs: Dry persistent cough, Fetal malformations, granulocytopenia, proteinuria (Rare).
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual  in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Contraindicated in CHF, Pulmonary diseases (Bronchial asthma/COPD), Peripheral vascular disease and Variant angina.
Cardioprotective – especially helpful to prevent sudden cardiac death if given Post MI, along with ACEIs.
Hypoglycemic episodes – (1 selective less risky)
Absence of SEs like Postural Hypotension, GIT effects etc
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual  in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Almost obsolete drugs
Reserpine – R.serpentina roots. Indigenous. Inhibits tpt of NA into storage granules  depletion. Slow onset (2-3 wks). Also CA & 5HT depletion in brain  depression, antipsychotic effect & Parkinsonism like symptoms. Not preferred as anti-HT drug now.

Guanethidine – Displaces NA from storage granules, release of NA from nerve terminals & NA reuptake inhibited  depletion. Obsolete drug.
Latest guidelines (JNC8, NICE 2011): Consider:-
Age / Race: Younger patients (↑ renin) respond better to ACEIs/ARBs. Blacks & aged respond better to CCBs. Diuretics alternatives to CCBs.
If monotherapy ineffective – ACEIs/ARBs + CCBs/Diuretics.
ACEIs/ARBs + CCBs + Diuretics – 3rd step
If all fails – resistant HT – add a aldosterone antagonist or beta-blocker with vasodilator action.
BP > 140/90 in pregnancy can be risky
CKD, Diabetes & Chronic HT are risk factors for Pre-eclampsia
Aspirin

1. Advantages Disadvantages More effective in elderly: also in patients with isolated systolic hypertension. Electrolyte imbalance Long acting, used once a day Metabolic: hyperglycemia, hyperlipidemia, hyperuricemia. No tolerance and no fluid retention Erectile dysfunction Reduce calcium excretion, preferred in osteoporosis (especially older women) Not effective in chronic renal disease. DIURETICS

2. Uses- Hydrochlorothiazide is one commonly used thiazide and consider as 1 st choice. the main problem with thiazide is hypokalemia and this can be avoided by K+ supplementation or using K+ sparing diuretics. However, ACEI/ARBs should not combined with K+ sparing diuretics which cause dangerous hyperkaliemia in some pt.

3. Indications : HT , especially co-existing with:- DM, Nephropathy, Left Ventricular Hypertrophy (LVF), Chronic Heart Failure (CHF), Angina, Post Myocardial Infarction (MI) cases. ADRs : Dry persistent cough, Fetal malformations, granulocytopenia, proteinuria (Rare). 4 ACEIs

4. Mechanism of action B locking voltage sensitive L-type Ca ++ channels (Long lasting current channels) in Blood Vessels  Ca ++ entry in smooth muscle cells of BVs Reduced depolarization Relaxation  PVR by arteriolar vasodilatation & mild venous dilatation 5 Ca ++ CHANNEL BLOCKERS 1 st line drugs

5. Advantages Disadvantages No sedation Short acting Safe in Bronchial Asthma, Variant Angina, Peripheral Vascular Disease. Renal perfusion maintained Hypertension associated with ischemic heart diseases and post MI CCBs not preferred Male sexual function maintained No effect on plasma lipids, Uric Acid, electrolytes, Hypertension associated with ischemic heart diseases and post MI do not improve survival. No teratogenicity  safely used in pregnancy [mild tocolytic (+)] Ca+ channel blockers

6. Efficacy as monotherapy ~30-40%. Always combined with other drugs Slow onset (1-3 weeks), well sustained action Gradual  in BP in hypertensives only. Mech : Initially, TPR increases due to -blockade Later TPR decreases – resistance vessels adapt to chronically decreased CO Both systolic & diastolic BP reduced. Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney ( 1 ). 7 BETA BLOCKERS

7. Advantages Disadvantages Absence of SEs like Postural Hypotension, GIT effects etc Unfavorable lipid profile (TGs/LDL) No salt & water retention Decreased work capacity / libido Cheap; once a day administration Hypoglycemic episodes – ( 1 selective less risky) Cardioprotective – especially helpful to prevent sudden cardiac death if given Post MI, along with ACEIs. Contraindicated in CHF, Pulmonary diseases (Bronchial asthma/COPD), Peripheral vascular disease and Variant angina. BETA blockers

8. Advantages Disadvantages Improved carbohydrate metabolism – suitable for DM except with neuropathy - high risk of postural hypotension. First dose Effect Improved lipid profile / no alteration of exercise capacity blurred vision Symptomatic relief of co-existing BPH / PVDs ejaculation in males Palpitations ALPHA blockers

9. Almost obsolete drugs Reserpine – R.serpentina roots. Indigenous. Inhibits tpt of NA into storage granules  depletion. Slow onset (2-3 wks ). Also CA & 5HT depletion in brain  depression, antipsychotic effect & Parkinsonism like symptoms. Not preferred as anti-HT drug now. Guanethidine – Displaces NA from storage granules, release of NA from nerve terminals & NA reuptake inhibited  depletion. Obsolete drug. 10 ADR NEURONE BLOCKERS

10. Treating Hypertension : Important clinical aspects Latest guidelines (JNC8, NICE 2011): Consider:- Age / Race: Younger patients (↑ renin) respond better to ACEIs/ARBs. Blacks & aged respond better to CCBs. Diuretics alternatives to CCBs. If monotherapy ineffective – ACEIs/ARBs + CCBs/Diuretics. ACEIs/ARBs + CCBs + Diuretics – 3 rd step If all fails – resistant HT – add a aldosterone antagonist or beta-blocker with vasodilator action 11

11. HT in Pregnancy BP > 140/90 in pregnancy can be risky CKD, Diabetes & Chronic HT are risk factors for Pre-eclampsia Aspirin 80-100mg/d Contraindicated drugs : ACEIs, Diuretics, Non-selective beta-blockers, Nitroprusside Drugs permitted : Labetalol (preferred), Nifedipine SR, Methyldopa, Hydralazine Titrate dosage for optimal response 12

12. Hypertensive Emergencies Controlled but rapid reduction of BP mandatory To be reduced to 160/100 mm Hg initially Nicardipine (preferred, 1 st line) – in combination with Labetalol/Esmolol to prevent reflex tachycardia. 5mg/ hr I/v infusion; can be titrated up to 15mg/hr. Sod Nitroprusside – 2 nd line. 13

13. Hypertensive Emergencies Glyceryl trinitrate – mainly useful in severe HT associated with ACS or MI. Combined with Labetalol/Nicardipine. 5-20µg/min I/v infusion. Avoided in stroke. Onset: 2-5 mins. Esmolol – Short acting β 1 blocker. Onset: 1-2 mins; Duration: 10-20 mins. 0.5mg/kg I/v bolus dose; 50-200µg/kg/min I/v infusion subsequently, combined with Nicardipine/Nitroprusside. Preferred in aortic dissection. 14

14. Hypertensive Emergencies (Oral drugs) Labetalol – 100-200 mg BD. Amlodipine – 10mg, repeated after 12 hrs. Captopril – 25mg. Not preferred Clonidine - 100µg every 1-2 hrs. Not preferred. 15

15. Clinical Case Study A 35 year old multiparous lady, in the 36 th week of pregnancy, complaining of mild to moderate headache with occasional episodes of breathlessness was found to have a blood pressure of 166/98 mm Hg on repeated recordings. She was treated for hypertension with pregnancy in her earlier pregnancy too. Though there was no history of Diabetes in the past, the lady has an altered glucose tolerance test. There were traces of albumin in the urine, but no glucose. Blood urea was 20 mg /dl and Serum creatinine was 0.6 mg/dl. All other lab reports were WNL. Routine ante-natal exam and USG did not reveal any fetal abnormalities. How will you manage this case? Which drugs can be used and why? 18

16. Question 1 Mark the wrong match about antihypertensive drugs and its mechanism. Clonidine-central α ₂ agonist Hydralazine- direct vasodilator Amlodipine- calcium channel blocker Losartan- ace inhibitor

17. Question 2 Which of the following drug is preferred for treatment of hypertensive emergency? Nicardipine Enalapril Spironolactone Propranolol

18. Question 3 Which of the following antihypertensive drug is avoided during pregnancy? Labetalol α-Methyldopa Lisinopril Nifedipine

19. Question 4 All of the following drugs are used for pulmonary hypertension Except Sildenafil Fenoldopam Epoprostenol Bosentan

20. Question 5 Which of the following antihypertensive drug causes sedation? Clonidine Hydralazine Candesartan Amlodipine

21. Question 6 All of the following statement are correct EXCEPT Hydrochlorothiazide is suitable agent in hypertension in patients with osteoporosis Lisinopril is considered first line drug in hypertension Prazosin is preferred in hypertension in patients with prostatic hypertrophy Propranolol is preferred for hypertension in patients with diabetes