Anti Hypertensive Drugs 2 Flashcards
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
• ACEI inhibit the activity of ———, an enzyme responsible for the conversion of ——— into ———, a potent ———.
• ——— is a prototype.
• They are given how many times daily and produce good — -hour BP control.
• Very beneficial in patient with——, ——, and ——- by preventing rapid progression and complications
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
• ACEI inhibit the activity of angiotensin-converting enzyme(ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.
• Captopril is a prototype.
• They are given once daily and produce good
24-hour BP control.
• Very beneficial in patient with heart failure, diabetes, and CKD by preventing rapid progression and complications
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Mechanism of action
• ACE catalyses the cleavage of a pair of amino acids from short peptides, thereby ‘converting’ the inactive ——— angiotensin I to the potent ——— angiotensin II .
• It also inactivates ——— – a vasodilator peptide.
• ACEI lower blood pressure by reducing ———- and perhaps also by increasing ———- peptides, such as ———.
• Angiotensin II causes ——— secretion from the zona glomerulosa of the ——— and inhibition of this contributes to the antihypertensive effect of ACE inhibitors.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Mechanism of action
• ACE catalyses the cleavage of a pair of amino acids from short peptides, thereby ‘converting’ the inactive decapeptide angiotensin I to the potent vasoconstrictor angiotensin II .
• It also inactivates bradykinin – a vasodilator peptide.
• ACEI lower blood pressure by reducing angiotensin II and perhaps also by increasing vasodilator peptides, such as bradykinin.
• Angiotensin II causes aldosterone secretion from the zona glomerulosa of the adrenal cortex and inhibition of this contributes to the antihypertensive effect of ACE inhibitors.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Pharmacokinetics
• ACE inhibitors are all active when administered ——-, but are highly —— and are eliminated in the ——.
• Enalapril are ——— and require metabolic conversion to active metabolites (e.g. ———).
• Many of these agents have long ——- permitting how many a daily dosing; ——— is an exception.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Pharmacokinetics
• ACE inhibitors are all active when administered orally, but are highly polar and are eliminated in the urine.
• Enalapril are prodrugs and require metabolic conversion to active metabolites (e.g. enalaprilat).
• Many of these agents have long half-lives permitting once daily dosing; captopril is an exception.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Adverse effects
– First-dose:———.
– Cough – Usually dry cough, due to accumulation of ———-
– Angio-oedema and Urticaria – due increased ——-
– Proteinuria – attributable to its ——— group
– Taste abnormality
– Pregnancy; fetal anomaly, so it is contraindicated in pregnancy – Renal failure (Functional) – in bilateral renal artery stenosis
– Rash
– Hyperkalaemia
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Adverse effects
– First-dose hypotension.
– Cough – Usually dry cough, due to accumulation of bradykinin – Angio-oedema and Urticaria – due increased kinin
– Proteinuria – attributable to its sulphhydryl group
– Taste abnormality
– Pregnancy; fetal anomaly, so it is contraindicated in pregnancy – Renal failure (Functional) – in bilateral renal artery stenosis
– Rash
– Hyperkalaemia
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Adverse effect will be :
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI)
Adverse effects
– First-dose hypotension.
– Cough – Usually dry cough, due to accumulation of bradykinin – Angio-oedema and Urticaria – due increased kinin
– Proteinuria – attributable to its sulphhydryl group
– Taste abnormality
– Pregnancy; fetal anomaly, so it is contraindicated in pregnancy – Renal failure (Functional) – in bilateral renal artery stenosis
– Rash
– Hyperkalaemia
CALCIUM-CHANNEL BLOCKERS
• Calcium channel blockers (CCB) block the entry of ———- into ———- cells in artery walls blocking———- channels.
• used to treat ——— and ———— as well as hypertension.
• Divided how many Classes.
• They are ———— relaxant.
CALCIUM-CHANNEL BLOCKERS
• Calcium channel blockers (CCB) block the entry of calcium into muscle cells in artery walls blocking voltage-dependent Ca2 channels.
• used to treat angina and supraventricular tachydysrhythmias as well as hypertension.
• Divided 2 Classes.
• They are smooth muscle relaxant.
CALCIUM-CHANNEL BLOCKERS
Mechanism of action
• Calcium-channel blockers inhibit Ca2 influx through voltage-dependent —- -type calcium channels.
• Cytoplasmic Ca2 concentrations control the ——— state of ———-.
• Calcium-channel blockers therefore relax arteriolar ———-, reduce ——— and lower———
CALCIUM-CHANNEL BLOCKERS
Mechanism of action
• Calcium-channel blockers inhibit Ca2 influx through voltage-dependent L-type calcium channels.
• Cytoplasmic Ca2 concentrations control the contractile state of actomyosin.
• Calcium-channel blockers therefore relax arteriolar smooth muscle, reduce peripheral vascular resistance and lower arterial blood pressure.
Dihydropyridine
1. Drugs: Nifedipine
2. Effect on heart rate:
3. Adverse effect:
4. Comment:
A. Drug:Nifedipine
1. Effect on heart rate: increases
2. Adverse effect: Headache, flushing, ankle swelling
3. Comment: Slow-release preparations for once/twice daily use
Dihydropyridine
1. Drugs:Amlodipine
2. Effect on heart rate:
3. Adverse effect:
4. Comment:
Dihydropyridine
1. Drugs:Amlodipine
2. Effect on heart rate:null
3. Adverse effect:ankle swelling
4. Comment: Once daily use in hypertension, angina
Dihydropyridine
1. Drugs:Nimodipine
2. Effect on heart rate:
3. Adverse effect:
4. Comment:
Dihydropyridine
1. Drugs:Nimodipine
2. Effect on heart rate:increases
3. Adverse effect: Flushing, headache
4. Comment: Prevention of cerebral vasospasm after subarachnoid haemorhage
Benzothiazepine
- Drugs: Diltiazem
- Effect on heart rate:
- Adverse effect:
- Comment:
Benzothiazepine
- Drugs: Diltiazem
- Effect on heart rate:null
- Adverse effect: Generally mild
- Comment: Prophylaxis of angina, hypertension
Phenylalkylamine
- Drugs: verapamil
- Effect on heart rate:
- Adverse effect:
- Comment:
Phenylalkylamine
- Drugs: verapamil
- Effect on heart rate: decreases
- Adverse effect: Constipation; marked
negative inotropic action - Comment: dysrhythmias. Slow-release preparation for hypertension, angina
ß-ADRENOCEPTOR ANTAGONISTS – B Blockers
• Beta-blockers are sympatholytic drugs
• Binds → beta-adrenoceptors → block the binding of ———— and ———— to these receptors.
• β-Adrenoceptors are subdivided into
• β1-receptors (———),
• β2-receptors (———, ———) and
• β3-receptors (———, e.g. in ———).
• Cardioselective drugs (e.g. ——-) → inhibit β— -receptors with less effect on ——— and ——- β— -receptors.
ß-ADRENOCEPTOR ANTAGONISTS – B Blockers
• Beta-blockers are sympatholytic drugs
• Binds → beta-adrenoceptors → block the binding of norepinephrine and epinephrine to these receptors.
• β-Adrenoceptors are subdivided into
• β1-receptors (heart),
• β2-receptors (blood vessels, bronchioles) and
• β3-receptors (some metabolic effects, e.g. in brown fat).
• Cardioselective drugs (NAB Me)(e.g. atenolol, metoprolol, bisoprolol, nebivolol) → inhibit β1-receptors with less effect on bronchial and vascular β2-receptors.
ß-ADRENOCEPTOR ANTAGONISTS
Mechanism of action
• Beta-adrenoceptors are coupled to a G— -proteins activate → adenylyl cyclase → cAMP from ATP.
• Increased cAMP activates → cAMP-dependent protein kinase (PK-A) that → phosphorylated — -type calcium channels → calcium entry into the cell. →
• sarcoplasmic reticulum in the heart; → these actions increase ——- (contractility).
• B Blockers blocks action above
ß-ADRENOCEPTOR ANTAGONISTS
Mechanism of action
• Beta-adrenoceptors are coupled to a Gs-proteins activate → adenylyl cyclase → cAMP from ATP.
• Increased cAMP activates → cAMP-dependent protein kinase (PK-A) that → phosphorylated L-type calcium channels → calcium entry into the cell. →
• sarcoplasmic reticulum in the heart; → these actions increase inotropy (contractility).
• B Blockers blocks action above
ß-ADRENOCEPTOR ANTAGONISTS
• Gs-protein activation also increases ——— (chronotropy).
• PK-A also phosphorylates sites on the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ———- receptors (———, ——- channels) associated with the sarcoplasmic reticulum.
• This provides more calcium for binding the troponin-C, which enhances inotropy.
• Finally, PK-A phosphorylates myosin light chains, which may contribute to the positive inotropic effect of beta-adrenoceptor stimulation.
ß-ADRENOCEPTOR ANTAGONISTS
• Gs-protein activation also increases heart rate (chronotropy).
• PK-A also phosphorylates sites on the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine receptors (ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic reticulum.
• This provides more calcium for binding the troponin-C, which enhances inotropy.
• Finally, PK-A phosphorylates myosin light chains, which may contribute to the positive inotropic effect of beta-adrenoceptor stimulation.
ß-ADRENOCEPTOR ANTAGONISTS
• β-Adrenoceptor antagonists reduce ———(via negative ——— and negative ——— effects on the heart),
• inhibit ——— secretion and some have additional central actions reducing ——- outflow from the central nervous system (CNS).
ß-ADRENOCEPTOR ANTAGONISTS
• β-Adrenoceptor antagonists reduce cardiac output (via negative chronotropic and negative inotropic effects on the heart),
• inhibit renin secretion and some have additional central actions reducing sympathetic outflow from the central nervous system (CNS).
Drug:propranolol
Selectivity :
Pharmacokinetic features:
Comment:
Drug:propranolol
Selectivity :non selective
Pharmacokinetic features: Non-polar; substantial presystematic metabolism; variable dose requirements;
multiple daily dosing
Comment: First beta-blocker in clinical use
