CVS Chem Flashcards
most widely used organic nitrate is
The most widely used is glyceryl trinitrate (GTN), but the group includes pentaerythrityl tetranitrate (PETN), isosorbide mononitrate (ISMO) and isosorbide dinitrate (ISDN).
Organic nitrates
All are explosive but require detonation and the explosive nature has not restricted their use in medicine.
GTN was used in the early experiments to identify EDRF as NO. As GTN requires metabolism to convert it into NO it was fortunate that this occurred within the tissue used for the initial experiments.
GTN uses and side effects
- Uses: - Prophylaxis & treatment of angina (Sublingually, 0.3-1.0 milligrams; i.v. infusion 10-200 micrograms/min; transdermal, 5mg/24h)
- Side effects: - Postural hypotension, throbbing headache & application site reactions with transdermal patches
• ISDN and ISMN uses
• Uses:
- ISDN for prophylaxis and treatment of angina (oral, 30-120 milligrams, up to 240 milligrams for left ventricular failure; i.v. infusion, 2-10 milligrams/hr up to 20 milligrams/hr)
- ISMN for heart failure and also for angina (oral 20 milligrams 2-3 times a day up to 120 milligrams daily in divided doses)
• ISMN is the active metabolite of ISDM
how does GTN work
GTN in the treatment of Angina
- Administration by puffer or under the tongue
- GTN Glyceryl trinitrate
- Taken into the bloodstream
- Converted by enzyme(s)
- NO. is released
major drawback of GTN
TOLERANCE CAN BE CONSIDERED A MAJOR
DRAWBACK
Amyl nitrite
- Organic nitrites are powerful vasodilators and have been used clinically for the relief of the symptoms of angina for well over 100 years
•Used to treat angina
•Too volatile to be convenient
•Commonly used in the 60’s as a recreational drug
The importance of pKa
o Drug absorption is determined by solubility, molecular
weight and the degree of ionisation
o The local pH will dictate the degree of drug ionisation
- pKa values for weak acids (HA) that exceed 10 to 11 = little, if any, anionic contribution in the pH ranges used in pharmaceutical formulations & in the physiological pH ranges.
- Similarly, pKa values for the conjugate acid of a weak base (BH+) that are below 2 to 3 = little, if any cationic contribution.
For a weak acid, HA
o At a pH above its pKa the acid exists mostly as A–
o At a pH below its pKa the acid exists mostly as HA (unionised)
For a weak base, B
o At a pH above its pKa the base exists mostly as B (unionised)
o At a pH below its pKa the base exists mostly as BH+
CVS drugs - selective
- β adrenergic antagonists
- Relatively β1 selective antagonists (cardioselective)
- Used to treat angina
- atenolol, bisoprolol, metoprolol
CVS drugs - non-selective
- Non-selective β adrenergic antagonists
- Used to treat angina
- propranolol, sotalol
CVS drugs - anti platelet and anticoagulant
- Inhibits platelet aggregation
- Used to treat angina
- Used as an anticoagulant
- aspirin, warfarin
α2 adrenergic agonist
- Clonidine is an α2 adrenergic agonist
- Inhibits sympathetic output from the CNS
- Used to treat hypertension
- Clonidine: R = H some passage into the CNS
- 4-Hydroxyclonidine: R = OH no passage into the CNS
- Apraclonidine: R = NH2 no passage into the CNS
Statins
- Statins inhibit synthesis of cholesterol
- Used to reduce cardiovascular disease
- Simvastatin, Lovastatin, Pravastatin
