Pharm Drugs - Even Lectures

• Lecture: Anti-HTN Drugs
• Angiotensin System Blockers
• Little or no increase in heart rate
• Reduce maladaptive ventricular hypertrophy   
• Side effects: cough, angioedema and rash 
• Overall a very safe class of drugs
• Contraindication: pregnancy
• Prototype: Captopril (‘pril’ suffix signifies ACE inhibitor)

• Lecture: Anti-HTN
• Beta-Blockers
• Side effects: bronchoconstriction due to beta-2 receptor blockade (propanolol is a non-selective beta-antagonist)
• Effects: decrease CO, reduce renin release, decrease TPR (after weeks), blunt reflexes caused by vasodilators (decrease baroreceptor induced reflex tachycardia)

• Lecture: Anti-HTN drugs
• Calcium Channel Entry Blockers (CCBs)
• Bind receptors on Ca channels in cardiac and smooth muscle cells
• Prevent Ca influx into smooth muscle --> decrease TPR
• Prevent Ca influx into cardiac cells --> potential for decreased HR, slowed AV conduction and decreased inotropy
• Mild side effects
• Can cause reflex tachycardia in response to hypotension caused by vasodilation
• May be combined with a beta-blocker
• Act selectively on arterioles (not veins)
• Postural hypotension is rare
• Gingival hyperplasia side effect

• Lecture: Anti-HTN drugs
• Diuretics
• First line drug
• Natriuretic (discharge of Na through urine)
• Acute effects: decrease plasma volume --> decrease CO
• Chronic effect: decrease TPR
• K "sparing" diuretics

Lecture: Anti-HTN drugs

• Endogenous Vasoactive Agents
• Released from vessel intima (ECs)
• Activates guanylyl cyclase
• Drug target: Increase production of or supply NO

Lecture: Anti-HTN drugs

Endogenous Vasoactive Agents

• Lecture: Anti-HTN drugs
• Endogenous Vasoactive Agents
• Caution - administration of NSAIDs can potentially increase AP

• Lecture: Anti-HTN drugs
• Endogenous Vasoactive Agents
• Contribute to ACE inhibitor effects

Lecture: Anti-HTN drugs

• Alpha-1 Adrenergic Blockers
• Causes both arterial and venous vasodilation
• Side effects: Postural hypotension (drugs that dilate veins directly OR prevent release or action of NE) and reflex tachycardia
• Usually taken with a diuretic
• Beta-blockers should also be co-administered

Lecture: Anti-HTN drugs

• Direct acting vasodilators
• K channel agonist
• Act directly on VSM
• Little effect on veins so little orthostatic hypotension
• Used for most refractory cases; only in combo with beta-blockers and usually with a diuretic
• Side effects: reflex tachycardia and edema

Lecture: Anti-HTN drugs

• Direct acting vasodilators
• Now used in combo with a nitrate
• Act directly on VSM
• Little effect on veins so little orthostatic hypotension
• Used for most refractory cases; only in combo with beta-blockers and usually with a diuretic
• Side effects: reflex tachycardia and edema

Lecture: Anti-HTN drugs

• Peripherally Acting Sympathomimetics
• Drugs that interfere with the storage and/or release of NE
• Older drugs that have severe side effects and only rarely used now for HTN
• Depletes stores of NE from neurons in both the CNS and PNS
• Decreases in NE release from post-ganglionic SNS neurons reduces PR and dilates veins
• Side effects: sedation, orthostatic hypotension, high incidence of depression

Lecture: Anti-HTN drugs

• Centrally Acting Alpha-2 Agonists
• Advantage - dont cause postural hypotension
• Decrease HR (lowering CO) and TPR --> decreased AP
• Side effects: hypertensive rebound if there is an abrupt withdrawl of drug, dry mouth, sedation
• Considered a second-line drug or for special cases (ie pregnant HTN pts)
• Clonidine acts as a parent compound in CNS
• a-methyl-DOPA converted to a-methyl NE

Lecture: Anti-anginal drugs

• Organic nitrates
• Overall effect: relaxation of most smooth muscle and decrease platelet aggregation
• Mechanism: GTN --> increased NO in VSM
• Directly acting vasodilators - nitrates increase NO synthesis within cells, nitroprusside releases NO
• Nitrovasodilators increase VSM NO --> Activation of guanylate cyclase --> increase cGMP --> stimulation of a cGMP-dependent kinase --> decreased intracellular Ca, Ca desensitization, opening of K channels --> relaxation of VSM

• Hemodynamics:
• Decreased AP (due to decreased PR and CO)
• LVEDP and thereby CO (due to venodilation)
• Possibly increase HR and contractility
• Total CBF usually not increased in pt with classical angina
• Distribution of CBF: improved to ischemic areas

Side effects: excessive decrease in AP with sildenafil use, orthostatic hypotension

• Do not dilate veins but useful for both classical and vasospastic angina
• Dilate coronary vessels - therefore useful for vasospastic angina; also dilate collaterals

Lecture: Anti-anginal

Reduce cardiac response to exercise, decrease sys BP, decrease HR, therefore decrease O2 demand

• Useful effects in angina/role:
• Prophylaxis
• Improve survival post MI
• Block reflex tachycardia

Lecture: Anti-anginal drugs

• Drugs for unstable angina
• unstable angina may reflect a non-occlusive thrombus on a plaque; may be related to impending plaque rupture and MI
• Clopidogrel (inhibits ADP mediated platelet aggregation), aspirin, CCB, GTN and anticoagulants used for unstable angina
• Lowering of LDL-cholesterol is critical; endothelial function recovers and plaque is stabilized

Lecture: anti-anginals

• 1st new class of antianginal drug approved for decades
• MOA is uncertain: change cardiac metabolism?
• Decrease Ca overload
• Decreases angina frequence and nitrate use
• Increases exercise tolerance
• Effective via oral route of administration

Lecture: Anti-anginal

• MOA is likely due to causing reduced HR
• Selective inhibitor of inward Na and K current during phase 4 (ie pacemaker current)
• Will decrease HR in excess of beta-ARX induced reduction
• Helpful for patients that can't tolerate BARX