Pharm MT 1 Drugs - OPT 6180

Hydrocholorthiazide (Microzide)

• preventing reabsorption in the DCT

• increased excretion of Na+, Cl-, K+, H2O

• INEFFECTIVE if GFR is low

• risk of dehydration and hypokalemia

Furosemide (Lasix)

• Loop diuretic → Inhibits Na+ and Cl- reabsorption in the ascending loop of Henle

• increased excretion of Na+, K+, Cl-

• EFFECTIVE even if GFR is low or kidney damage present

• most effective diuretic

spironolactone (Aldactone)

• direct antagonist of aldosterone

• inhibits ENac and Na+/K+-ATPase

• reduces NA+ reabsorption and K+ secretion

• potassium sparing

• vasodilator too (RAAS system)

Triamterene (Dyrenium, Amiloride)

• inhibit ENac on lumen membrane

• keeps Na+ in tubule to reduce abosrption

• potassium sparing

Chlorthalidone (Hygroton)

• preventing reabsorption in the DCT

• increased excretion of Na+, Cl-, K+, H2O

• INEFFECTIVE if GFR is low

loop diuretics to know (2)

Furosemide (Lasix), Bumetanide

thiazides to know (2)

Hydrochlorothiazide (Microzide), Chlorthalidone (Hygroton)

potassium sparing diuretics to know (3)

Spironolactone (Aldactone), Triamterene (Dyazide), Amiloride

side effects (2) of potassium sparing diuretics

hyperkalemia and endocrine effects (anti-androgen)

Lisinopril (Prinivil), Benazepril (Lotensin), Enalapril (Vasotec), Ramipril (Altace)

• ACE inhibitors → “pril”s

  • RAS antagonist

• blocks Angiotensin I → Angiotensin II

• blocks breakdown of bradykinin

side effects of ACE inhibitors

• hypotension

• dry cough

• hyperkalemia

name the ACE inhibitors (4)

• Lisinopril (Prinivil)

• Benazepril (Lotensin)

• Enalapril (Vasotec)

• Ramipril (Altace)

name the Competitive Angiotensin Receptor Antagonists (4)

“artan”s

• Losartan (Cozaar)

• Olmesartan (Benicar)

• Valsartan (Diovan)

• Irbesartan (Avapro)

Losartan (Cozaar), Olmesartan (Benicar), Valsartan (Diovan), Irbesartan (Avapro)

• Competitive Angiotensin Receptor Antagonists (“-ARTAN”s)

  • RAS antagonist

• directly binds Ang. II receptors and blocks vasoconstriction

• preference to AT1 receptor

• Tx for atherosclerosis and hypertension

side effects of competitive angiotensin receptor antagonists

hyperkalemia, hypotension

Aldosterone receptor antagonist (1)

spironolactone (RAS antagonist and diuretic)

Classes of drugs (2) that decrease peripheral vascular resistance (PVR) or cardiac output (CO)

nitrates and calcium channel blockers

Calcium channel vasodilators to know (4)

Nifedipine (Procardia XL), Amlodipine (Norvasc), Dilitazem (Cardizem CD), Verapamil (Isoptin)

what happens to the vasculature when more cGMP is synthesized?

upreg. MLCP → less myosin activated → relaxation of the vasculature

How do calcium channel blockers work?

Decreased calcium influx causes relaxation of smooth muscle, cardiac muscle, and blood vessels

low doses of what two drugs will cause primarily vasodilation, but in higher concentrations will cause both reduction of caridac work load and vasodilation

Dihydropyridines → Nifedipine and Amlodipine

What two CCB drugs will cause decreased cardiac output and vasodilation

Verapamil and Diltazem

adverse effects of calcium channel blockers

hypotension, headache, nausea, edema, palpitations, flushing, heart rate effects (Verapamil and Diltazem)

Sympatholytics - blocking selective adrenoreceptors

Beta blockers can diminish cardiac output and renin production

Beta-1 selective antagonists (2)

• Metoprolol (Lopressor, Toprol XL) and Atenolol (Tenormin)

  • most widely used

  • Tx of abnormal heart rhythm and secondary MI/heart attack protection

non-selective Beta antagonists (1)

Propanolol (Inderal)

• HTN treatment

• liver, cardiac, lungs

Why is Carvedilol (Coreg) not like other Beta Blockers/Antagonists?

Beta (non-selective) and Alpha blocking activity

• vasodilatory and cardio selective

• no reflexive tach thanks to Beta blocking

• CHF and HTN treatment

stimulation of alpha receptor causes an increase in…

increase in blood pressure

stimulation of beta-1 receptor

increased cardiac effect → increase HR and contractility

stimulation of beta-2 receptor

bronchodilation

Nitroglycerine

nitrate used in treat acute, variant angina in ischemic heart disease

• acute vasodilation (nitric oxide release from endothelium relaxes vascular smooth muscle) to decrease BP

• do NOT combine with other vasodilators/HTN Rx

Isosorbide Mononitrate

nitrate used to treat longer lasting angina symptoms

• longer vasodilaton and more stable than nitroglycerin

Side effects of nitrates

• orthostatic hypotension → reflex tach

• throbbing headache

• flushing

Drug classes that reduce cardiac workload and used to treat HF (3)

ACE inhibitors, B-blockers, vasodilators

Drugs that control excessive fluid and used to treat HF

diuretics

Drugs that enhance contractility and used to treat HF (3)

Digoxin, Sympathomimetics, PDE Inhibitors

classes of drugs used to treat ischemic heart disease (3) and goal of treatment

nitrates, CCBs, B-blockers

decrease demand and increase supply of O2

drug classes used to treat hypertension

diuretics (all), ACE inhibitors, Competitive Angiotensin Receptor Antagonists, Calcium Channel Blockers

heart failure drug Tx options (7)

ACE inhibitors, B-blockers, vasodilators, diuretics, Digoxin, Sympathomimetics, PDE Inhibitors

Anti-Arrythmia Drugs - Class I definition and examples (3)

Sodium channel blockers

blocks Na+ entry during depolarization and slows depolarization in fast AP cells (atria, ventricles, His/Purkinje bundles)

• Lidocaine, Flecainide, Propafenone

Anti-Arrythmia Drugs - Class II definition and example (1)

increase action potential duration and effective refractory period

Beta Blockers → propranolol for tachycardia

blocks Na+ entry during depolarization and slows depolarization in slow AP cells (sinus and AV nodes)

Anti-Arrythmia Drugs - Class III definition and example (1)

Potassium channel blockers prolong the repolarization phase by blocking efflux of K+

• Amidarone (coradarone)

Class II Antiarrhythmic drug side effects

Hypotension, bradycardia

Class I Antiarrhythmic drug side effects

blurred vision

Class III Antiarrhythmic drug side effects

corneal deposits of Rx

Anti-Arrythmia Drugs - Class IV definition and examples (2)

blocking inward calcium current → calcium channel blockers predominantely used for atrial arrythmias

• Verapamil

• Diltiazem

Anti-Arrythmia Drug - Unclassified

Adenosine used for paroxysmal supraventricular tachycardia

• extremely short half life, IV only

• hyperpolarization by increase K+ conductance and decrease Ca2+ influx

anti-platelet drugs (2) and side effects

NSAIDs → Aspirin

Clopidogrel (Plavix) → P2Y12 ADP receptor blocker

• uncontrolled bleeding

• reminder that these have NO effect on existing clots/thrombi

Anti-Platelet NSAID: name and MOA

Aspirin

• irreversibly binds COX enzyme

• decrease thromboxane (TxA2) aggregation

P2Y12 ADP Receptor Blocker: name and MOA

Clopidogrel (Plavix) works by inactivating the platelet P2Y12 ADP receptor, which is responsible for amplification and stabilization of platelet aggregation and clot formation (see pic)

Anticoagulants (5) - definition and names

• provides prophylaxis against of venous and arterial thrombosis

Warfarin (Coumadin), Heparin, Fondaparinux, Rivaroxaban (Xarelto), Apixaban (Eliquis)

Warfarin (Coumadin) MOA and side effects

Vitamin K inhibitor

• vit. K is required for coagulation cascade factor activation

• factors that have already been activated are NOT affected, delay in onset of Warfarin

• side effect: hemorrhage

Rivaroxaban (Xarelto) & Apixaban (Eliquis) MOA and side effects

Direct factor Xa inhibitors → no thrombin formation

side effect: hemorrhage

Anemia and Treatments (4)

low concentration of hemoglobin and RBCs

Iron, Cyanocobalamin (Vitamin B12), Folic Acid, Darbepoetin alfa

what type of anemia does iron treat?

iron deficiency anemia

what type of anemia does Vit B12/Cyanocobalamin and/or folic acid treat?

Vit B12, Folate, and Megaloblastic anemia

What is Darbepoetin alfa (Aranesp)?

Tx for anemia → hematopoietic growth factor (recombinant erythropoietin)

5 types of dyslipidemia treatments

1. Derivatives of fibric acid (fibrates)

2. Nicotinic Acid

3. Bile Acid sequestrants

4. Inhibitors of HMG CoA Reductase (statins)

5. Cholesterol Absorption inhibitors

Dyslipidemia treatment name, MOA, and side effects: Fibric acid derivatives (2)

Decrease hepatic triglyceride production

• Gemfibrozil (Lopid)

• Fenofibrate (Tricor)

SEs: GI disturbances

Dyslipidemia treatment name, MOA, and side effects: Bile Acid Sequestrants (3)

Bind bile acids & remove from enterohepatic circulation (excreted in feces) → Lowers LDLs, raises HDLs

• Cholestipol (Colestid)

• Cholestyramine (Prevalite)

• Colesevelam (Welchol)

Side Effects:

• Constipation, Diarrhea, Bloating, Flatulence, Bind fat-soluble vitamins

HMG CoA reductase inhibitors (5) MOA and side effects

Decreasing LDL synthesis and increasing LDL receptors in the liver

• PRAVASTATIN (Pravachol)

• SIMVASTATIN (Zocor)

• ATORVASTATIN (Lipitor)

• ROSUVASTATIN (Crestor)

• LOVASTATIN (Mevacor)

SEs: myalgia - muscle aches and pains, teratogenic - harmful for fetal development

Dyslipidemia treatment and MOA: cholesterol absorption inhibitors (1)

Prevents cholesterol reuptake in the small intestine by blocking cholesterol transport and inhibiting reabsorption of cholesterol excreted in bile

• Ezetimibe (Zetia)

Alirocumab and Evolocumab are used to control cholesterol. How do they do this?

Monoclonal antibodies inhibit the PCSK9 protein, allowing LDL receptors to be recycled (instead of degraded). The PCSK9 protein is responsible for degrading LDL receptors that clear LDL cholesterol, so inhibition will promote LDL receptors to clear cholesterol from plasma.