CVS DRUGS

• Sympathomimetics agents

  Drugs that mimic the effects of the sympathetic nervous system
• DRUGS

  • Epinephrine (Adrenaline)
  • Norepinephrine
  • Ephedrine & Pseudoephedrine
  • Clonidine
  • Phenylephrine, oxymetazoline
  • Dobutamine
  • Dopamine
  • Amphetamine
  • Tyramine
  • Isoprenaline
  • Salbutamol, terbutaline (SABA)
  • Salmeterol, formoterol (LABA)
• MOAof epinephrine

  • A&B nonselective
  • CVS: B1 receptors
  • blood vessels: post-sy A receptor
  • Lungs: Bronchial muscle relaxation by stimulation of ß2 receptors
  • Skeletal muscle - ß2 receptors
  • Uterus ʹ ß2 receptor
  • Bladder, urethral sphincter & prostate - A1A
  • Metabolic ʹ Hyperglycaemia
  • CNS: Does not cross BBB
  • Eye ʹ A1 receptor
• ADME of Epinephrine

  • Oral
  • Poor bioavailability due to first pass metabolism
  • Routes: SC, IM, Topical, Intracardiac, Inhalational, IV
• Uses of Epinephrine

  • Bronchial asthma, Anaphylactic shock, Cardiac arrest, Epistaxis / bleeding from gums, With local anaesthetics, Glaucoma
• ADR of Epinephrine


  • Tachycardia, palpitation, anxiety, tremor, Cerebral haemorrhage due to marked raise in BP, ventricular arrhythmias
• Norepinephrine


  A, ß1 agonist, sympathetic neurotransmitter
• Ephedrine & Pseudoephedrine

  ADME: Less potent and longer acting as not metabolized by MAO & COMT, Orally effective

  Uses:Nasal decongestant in common cold,

  ADR:CNS stimulation
• Clonidine


  A2 agonist, Decr. Sym activity

  Used in hypertension, drug addiction, menopausal hot flushes
• Phenylephrine, oxymetazoline


  A1 agonist vasoconstriction, Used IV-shock (hypotension), Topical decongestants, Topical mydriatics
• Dobutamine


  B1 stimulant, +ve inotropic, No incr. PR&BP, No incr. O2 requirement by heart,

  Used in cardiogenic shock due to acute heart failure in MI or following cardiac surgery
• Dopamine


  D1 more sensitive, B1 &A1 stim at high doses

  -Low dose = renal vasodilatation with incr. in renal perfusion & urine formation

  -High dose = Myocardial stimulation &incr. in BP, Still higher dose= vasoconstriction &rise in BP

  -Used in shock, CCF with oliguria, Renal failure
• Amphetamine


  More cns effects: CNS- alertness, increased conc., work

  capacity

  -Orally active & long acting

  -Used in narcolepsy, appetite suppressant in obesity, ADHD in children
• Tyramine


  Met by MAO, Tachyphylaxis, Hypertensive crisis occurs in patients receiving MAOI (antidepressants)
• Isoprenaline


  B1 &2 nonselective, Short DOA,

  Cardiac toxicity in therapeutic dose
• Salbutamol, terbutaline (SABA)


  B2 selective, Bronchodilatation & decreased release of mediators of inflammation, Skeletal muscle blood vessels dilatation, Uterine relaxation, Cardiac stimulation ʹ negligible with therapeutic doses, but in high doses may be significantly high, Resistant to met by MAO & COMT ʹ longer acting than adrenaline (DOA-3h), Oral, Inhalation through inhalers, nebulisers (10%), Used in bronchial asthma
• Salmeterol, formoterol (LABA)


  B2 selective, Bronchodilatation & decreased release of mediators of inflammation, Skeletal muscle blood vessels dilatation, Uterine relaxation, Cardiac stimulation ʹ negligible with therapeutic doses, but in high doses may be significantly high, Inhalational, slow onset of action and longer DOA (12h), Used for prevention of nocturnal asthma, mostly FDC with inhaled corticosteroid
• ADR of Sympathomimetics


  • Fine tremors of fingers ʹ gradually tolerance develops, Palpitation, Restlessness & anxiety etc, LABA: excess medication leads to cardiac toxicity
• Sympatholytic agents


  Drugs that block the effects of the sympathetic nervous system
• Sympatholytic drugs

  • Prazosin, Terazosin, tamsulosin
  • Yohimbine
  • Propranolol, timolol (nonselective)
  • Metoprolol, atenolol
  • Labetalol
  • Carvedilol
• MOA


  • Prazosin, Terazosin, tamsulosin: A1 selective, Vasodil ʹ fall in PR & BP & incr. blood flow to organs, Incr. RBF, Relaxation of bladder neck & prostatic capsule, facilitate urine flow
  • Yohimbine: Presy A2 ʹ incr. release of NE, Heart ʹ tachycardia, incr. in COP & BP, Postsy A2 ʹ similar to A1 ʹ vasodil, fall in BP
  • Propranolol, timolol: Dec. HR &FOC ʹ dec. COP & BP, Dec. O2 req, Dec. renin secretion ʹ dec BP
  • Metoprolol, atenolol: Selective B1 blockers, Lungs: incr. bronchial resistance *no effect on pulmonary fx. (non-asthmatics)
  • Labetalol: Nonselective b blocker with a1 blockade, Vasodil, Comp antagonist both A1 &B
  • Carvedilol: Vasodil, Competitive antagonist both A1 &B, has inflam. and antioxidant actions
• ADME


  • Prazosin (10h), Terazosin (18h), Oral
  • Propranolol: absorption: oral, P (crosses CNS, first pass met)
• USES


  • Prazosin, Terazosin, tamsulosin: hypertension, hypertensive emergencies, peripheral vascular disease, cardiac failure, following extravasation of sympathomimetic amines after iv ad
  • Propranolol, timolol: hypertension, angina pectoris, MI, cardiac arrhythmias, mild/mod heart failure, nonCVS use: glaucoma (timolol), prophylaxis of migraine, benign essential tremor, hyperthyroidism, anxiety states, prevention of stage fright
  • Metoprolol, atenolol: hypertension, angina pectoris, MI, cardiac arrhythmias, mild/mod heart failure
  • Labetalol: hypertension, hypertensive emergencies, hypertension in pregnancy
  • Carvedilol: heart failure, hypertension
• ADR


  • Prazosin, Terazosin, tamsulosin: Reflex tachycardia, nasal congestion, sodium & water retention, impotence, Postural hypotension, "first dose phenomenon"
  • Propranolol, timolol: bradycardia, heart block, CHF, sedation, fatigue, depression, sleep alterations, bad dreams, sudden withdrawal leads to angina or MI, ADR due to B2 blockade (Resp distress, DM, cold extremities)
  • Metoprolol, atenolol: life threatening bronchoconstriction (asthmatics), DM (mask symptoms), Dec. intraocular pressure, decrease RBF ʹ sodium and water retention
• Hyperlipidaemic drugs


  Drugs used to treat high blood lipid levels
• DRUGS


  • HMG CoA reductase inhibitors (statins): Lovastatin, simvastatin, atorvastatin, rosuvastatin
  • Fibrates: Gemfibrozil, fenofibrate
  • Cholesterol absorption inhibitors: Ezetimibe
  • Bile acid binding resins: Cholestyramine, Colestipol
• HMG CoA reductase inhibitors (statins)


  X conversion of HMG-CoA to mevalonic acid, Decreased hepatic cholesterol synthesis, up-regulates LDL receptor synthesis, increasing LDL-C clearance from plasma into liver cells, reduce plasma LDL-C, reduction in plasma tg and increase in HDL-C, Simvastatin, lovastatin, and pravastatin (specific, reversible, competitive statins), Atorvastatin and rosuvastatin are long-lasting inhibitors, rapid first pass met
• Uses of statins


  • secondary prevention of MI & stroke, primary prevention of arterial disease, homozygous fam hyperch, severe drug-resistant dyslipidaemia (ezetimibe +statin)
• ADR of statins


  • Myalgia, Gastrointestinal disturbance, Raised hepatic enzymes, Insomnia, Rash, Serious: severe myositis, angioedema, CI: pregnancy, nursing mother, children & teenagers
• Fibrates


  lower serum tg & increase HDL levels, Bind to peroxisome proliferatorʹactivated receptors (PPARɲͿΘŝŶĐƌĞĂƐĞĞdžƉƌĞƐƐŝŽŶŽĨ>WůŝƉĂƐĞ, reduction in circulating VLDL, and hence tg, LDL-C and incr. in HDL-C
• Uses of fibrates


  • hypertriglyceridemia, type III hyperlipidaemia
• ADR of fibrates


  • severe rhabdomyolysis with myoglobinuria and ARF, GI symptoms, pruritus & rash, clofibrate predispose to gallstones, renal failure, liver failure
• Cholesterol absorption inhibitors


  selectively inhibits absorption of dietary and biliary cholesterol in the small intestine, reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood, lowers LDL
• Uses of cholesterol absorption inhibitors

  • hypercholesterolaemia when statin CI, in addition to statin
• Bile acid binding resins


  anion-exchange resins that bind negatively charged bile acids and bile salts in the small intestine, Resin + Resin
• Uses of bile acid binding resins

  • hyperlipidaemia
• VLDL


  Very low-density lipoprotein
• LDL-C


  Low-density lipoprotein cholesterol
• HDL-C


  High-density lipoprotein cholesterol
• Conditions associated with hypertriglyceridemia


  • Hypertriglyceridemia
  • Type III hyperlipidaemia
  • Severe rhabdomyolysis with myoglobinuria and ARF
  • GI symptoms
  • Pruritus & rash