Pharm Exam 3

what is neuropharmacology?

the study of drugs that alter processes controlled by the nervous system

neuropharmacology is divided into 2 broad categories:

-peripheral nervous system drugs
-central nervous system drugs

neuropharmacologic drugs can modify:

-skeletal muscle contraction
-cardiac output
-vascular tone
-respiration
-GI function
-uterine motility
-glandular secretion
-ideation, mood, and perception of pain

what is axonal conduction?

action potential down the axon (local anesthetics)

what is synaptic transmission?

information carried across the neuron gap and the postsynaptic cell

give an example of a postsynaptic cell

another neuron, muscle cell, or cell within a secretory gland

receptors are specific for certain

transmitters

receptor activity is affected by

transmitter molecules

if there is no receptor for a given transmitter, what kind of effect will that transmitter produce?

no effect

drugs work by influencing:

receptor activity on target cells (mostly through affecting synaptic transmission

name the steps in synaptic transmission

1. transmitter synthesis
2. transmitter storage
3. transmitter release
4. receptor binding
5. termination of transmission

describe the effects of drugs on transmitter synthesis

-increase transmitter synthesis
-decrease transmitter synthesis
-cause the synthesis of transmitter molecules

describe the effects of drugs on transmitter storage

-cause receptor activation to decrease

describe the effects of drugs on transmitter release

-promote or inhibit release

describe the effects of drugs on receptor binding

-cause activation
-block activation
-enhance activation

describe the effects of drugs on termination of transmission

-block transmitter reuptake
-inhibit transmitter degradation

what is the most desirable quality a drug can have?

selectivity (after effectiveness)

why is selectivity a desirable quality of drugs?

able to alter a disease process while leaving other physiologic processes largely unaffected

name and describe the divisions of the nervous system

-central nervous system: brain and spinal cord
-peripheral nervous system: somatic motor and autonomic (parasympathetic/sympathetic)

name the principal functions of the autonomic nervous system

-regulate the heart
-regulate secretory glands (salivary, gastric, sweat, and bronchial)
-regulate smooth muscles (bronchi, blood vessels, urogenital system, and GI tract)

name the regulatory functions of the parasympathetic nervous system

-slowing the heart rate
-increased gastric secretion
-emptying the bladder
-emptying the bowel
-focusing the eye for near vision
-constricting the pupil
-contracting bronchial smooth muscle

name the general therapeutic functions of drugs affecting the parasympathetic nervous system

-digestion of food
-excretion of waste
-control of vision
-conservation of energy

name the main functions of the sympathetic nervous system

-regulation of the CV system
-regulation of body temp
implementation of "fight-or-flight" reaction

name the homeostatic objectives of the SNS

-maintain blood flow to the brain
-redistribute blood flow during exercise
-compensate for loss of blood, primarily by causing vasoconstriction

what are sympathomimetic/lytic drugs primarily used for?

primarily used for effects on the heart and blood vessels and lungs

what are sympatholytic antagonists used for in the heart?

hypertension, angina pectoris, heart failure

what are sympathomimetic agonists used for in the heart?

heart failure

what are sympathomimetic agonists used for in the lungs?

primarily asthma

name and describe the neurotransmitters of the peripheral nervous system

-acetylcholine: employed at most junctions of the peripheral nervous system
-norepinephrine: released by most postganglionic neurons
-epinephrine: released by the adrenal medulla

name and describe the 2 basic categories of receptors in the peripheral nervous system

-cholinergic receptors: mediated by acetylcholine
-adrenergic receptors: mediated by epinephrine and norepinephrine

name the cholinergic receptor subtypes and their functions

-nicotinic n (neuronal): promotes ganglia transmission and promotes release of epinephrine
-nicotinic m (muscle): contraction of skeletal muscles
-muscarinic: activates target organs of the parasympathetic nervous system

name the adrenergic receptor subtypes and their functions

-alpha 1: vasoconstriction, ejaculation, contraction of bladder neck and prostate
-alpha 2: located in presynaptic junction, little clinical significance
-beta 1: heart - increases heart rate, force of contraction, and velocity of conduction in AV node; kidney - renin release
beta 2: bronchial dilation, relaxation of uterine muscle, vasodilation, and glycogenolysis
-dopamine: dilates renal blood vessels

epinephrine can activate all alpha and beta receptors, but not:

dopamine receptors

norepinephrine can activate alpha1, alpha2, and beta1 receptors but not:

beta2 or dopamine receptors

dopamine can activate

alpha1, beta1, and dopamine receptors

which neurotransmitter is the only one capable of activating dopamine receptors?

dopamine

what is the main difference between adrenergic agonists and antagonists?

-agonists: sympathomimetic
-antagonists: sympatholytic

what are adrenergic agonists used to treat?

CHF, asthma, preterm labor

what are the mechanisms of adenergic agonists?

-bind directly to receptors (most common)
-promote norepinephrine (NE) release
-block NE reuptake
-inhibit NE inactivation

name the classes of adrenergic agonists

-catecholamines
-noncatecholamines

describe catecholamines

-cannot be used orally
-brief duration of action
-cannot cross the blood-brain barrier (polar molecules)

describe noncatecholamines

-can be given orally
-metabolized slowly by MAO: longer half-life
-more able to cross the blood-brain barrier

describe receptor activity at low doses

activation with low doses is more selective, less selective with higher doses (cross over into other receptors)

name the therapeutic uses of alpha1 activation:

-vasoconstriction (most common use)
\---hemostasis: arrest bleeding via vasoconstriction
\---nasal decongestion: mucosal vasoconstriction
\---adjunct to local anesthesia: delays absorption of local anesthetic
\---elevation of BP: vasoconstriction
-mydriasis: dilation radial muscle of the iris

name the adverse effects of alpha1 activation:

-hypertension (widespread vasoconstriction)
-necrosis (treat with alpha1 blocking agent; ex. phentolamine)
-bradycardia (response to vasoconstriction and elevated BP)

name the therapeutic activation of alpha2 activation

-receptors in periphery: located presynaptically, activation inhibits NE release
-receptors in CNS: reduction of sympathetic outflow to heart and blood vessels (clonidine: antihypertensive, relief of severe pain)

name the therapeutic applications of beta1 activation

increases heart rate and force of contraction, therefore increasing cardiac output and improving tissue perfusion. This can be useful for:
-cardiac arrest (not preferred treatment)
-shock: positive inotropic effect; increases heart rate
-hypotension: promotes renin secretion / increases heart rate
-heart failure: positive inotropic effect
-atrioventricular heart block: enhances impulse conduction through AV node

name the adverse effects of beta1 activation

-altered heart rate or rhythm (tachycardias or dysrhythmias)
-angina pectoris (increased cardiac oxygen demand)

name the therapeutic applications of beta2 activation

-asthma: bronchodilation, decrease airway obstruction
-delay of preterm labor: relaxation of smooth muscle

name the adverse effects of beta2 activation

-hyperglycemia: promotes glycogenolysis, primarily a problem for diabetics
-tremor: most common side effect (activation of receptors in skeletal muscle enhances contraction)

name the therapeutic applications of dopamine receptor activation

-shock
-dilates kidney vasculature
-improves renal perfusion (circulation) promoting urine production which decreases risk of renal failure
-enhances cardiac contraction due to activating beta1 receptors in the heart

name the adverse effects of dopamine receptor activation

-tachycardia
-dysrhythmias
-anginal pain
-necrosis with extravasation

describe the pathophysiology of anaphylaxis

-severe allergic response
-hypotension, bronchoconstriction, edema of the glottis

what is the treatment of choice for anaphylactic shock?

epinephrine

epinephrine is a:

adrenergic agonist (catecholamine)

what types of receptors does epinephrine activate?

alpha1, alpha2, beta1, beta2

what is epinephrine used for?

-alpha1: delay absorption of anesthetics, control superficial bleeding, reduce nasal congestion, elevate BP, assist in eye procedures (mydriasis)
-beta1: overcome heart block, restore cardiac function in cardiac arrest
-beta2: asthma - promotes bronchodilation

describe the pharmacokinetics of epinephrine

-inactivation by enzyme MAO and COMT and uptake into adrenergic nerves
-administer topically, by injection, and inhalation (not oral)

name the adverse effects of epinephrine

-hypertensive crisis
-dysrhythmias
-angina pectoris
-necrosis
-hyperglycemia

name the drug interactions of epinephrine

-MAO inhibitors
-TCAs
-general anesthetics
-alpha or bets adrenergic blocking agents

describe the mechanism of adrenergic antagonists

direct, reversible blockade of adrenergic receptors

name the therapeutic applications of an alpha1 blockade

-essential hypertension
-benign prostatic hyperplasia
-overdose of agonist
-Raynaud's disease
-pheochromocytoma

name the adverse effects of an alpha1 blockade

-orthostatic hypotension
-reflex tachycardia
-nasal congestion
-inhibition of ejaculation
-sodium retention and increased blood volume

describe the selectivity of beta-adrenergic blocking agents

-nonselective: block beta1 and beta2 receptors (propranolol)
-cardioselective: blocks beta1 receptors (metoprolol)

name the therapeutic effects of beta1 blockade

-reduced heart rate
-reduced force of contraction
-reduced velocity of impulse conduction
-reduced renin secretion

name the therapeutic uses of beta1 antagonists

-angina pectoris
-hypertension
-cardiac dysrhythmias
-myocardial infarction
-heart failure
-migraine
-hyperthyroidism
-stage fright
-glaucoma
-pheochromocytoma

name the adverse effects of beta blockade

-beta1: bradycardia, reduced cardiac output, heart failure, AV heart block, rebound cardiac excitation
-beta2: bronchoconstriction, inhibits glycogenolysis

the suffix "olol" is usually a

beta blocker

describe the action of propranolol

-blocks beta1 and beta2 receptors
-beta1: reduces heart rate, decreases force of contraction, suppresses AV impulse conduction, suppresses renin secretion. Beta2: bronchoconstriction, vasoconstriction, inhibits glycogenolysis

describe the action of metoprolol

-cardioselective beta blocker (only beta1 blockade at therapeutic doses)
-reduces heart rate, force of contraction, AV conduction velocity, and renin secretion

name the functions of the circulatory system

-delivery of oxygen, nutrients, ect.
-removal of carbon dioxide
-removal of metabolic waste

name the divisions of the circulatory system

-pulmonary
-systemic

what is the cardiac output of the average adult?

5 L/min

what is the equation for cardiac output?

HR x SV \= CO

what is stroke volume?

the amount of blood ejected by the heart in any one contraction

what is preload?

end-diastolic volume/pressure

what is afterload?

arterial pressure the left ventricle must overcome to eject blood

what factors determine venous return?

-systemic filling pressure
-auxiliary muscle pumps
-resistance to flow between peripheral vessels and the right atrium
-right atrial pressure

what is the equation for arterial pressure (systolic BP)

peripheral resistance X cardiac output

arterial pressure is regulated by:

-autonomic nervous system
-renin-angiotensin system
-kidneys

what are the purposes of drugs acting on the RAAS?

-regulation of BP
-regulation of blood volume
-regulation of electrolyte balance
-mediation of pathophysiologic changes

what does renin do?

catalyzes formation of angiotensin I

what are the actions of aldosterone relating to the RAAS?

-regulation of BP and blood volume
-pathologic CV effects

describe the mechanism of action of Captopril

-inhibits the ACE needed to change the inactive angiotensin I to active angiotensin II, therefore decreasing the amount of angiotensin II
-increases bradykinin

name the therapeutic uses of captopril

-hypertension
-heart failure
-MI
-diabetic and nondiabetic nephropathy
-prevention of MI, stroke, and death in patients at high CV risk

name the adverse effects of ACE inhibitors

-first-dose hypotension
-fetal injury
-cough
-hyperkalemia
-renal failure
-neutropenia
-angioedema

what is the drug classification of captopril?

ACE inhibitor

name the drug interactions of ACE inhibitors

-diuretics
-antihypertensive agents
-drugs that raise potassium levels
-lithium
-NSAIDs

name the contraindications of ACE inhibitors

-pregnancy
-angioedema
-renal artery stenosis

what is the drug classification of valsartan?

angiotensin II receptor blocker (ARBs)

describe the mechanism of action of valsartan

-block access of angiotensin II
-cause dilation of arterioles and veins
-prevent angiotensin II from inducing pathologic changes from cardiac structure
-reduce excretion of potassium
-decrease release of aldosterone
-increase renal excretion of sodium and wtaer
-don not inhibit kinase II
-do not increase levels of bradykinin

name the therapeutic uses of ARBs (valsartan)

-hypertension, HF, MI
-diabetic nephropathy
-patient unable to tolerate ACE inhibitors: protection against MI, stroke, and death from CV causes in high-risk patients
-may prevent development of diabetic retinopathy
-new data show that ACE inhibitors and ARBS are not effective for primary prevention of nephropathy in normotensive diabetic patients

name the adverse effects of ARBs (valsartan)

-angioedema
-fetal harm
-renal failure
ARBs do not promote accumulation of bradykinin in the lung and therefore have a lower instance of cough

describe the mechanism of action of spironolactone

-blocks aldosterone receptors
-binds with receptors for other steroid hormones

name the therapeutic uses of spironolactone

-hypertension
-HF

name and describe the 2 types of calcium channel blockers (diltiazem)

-nondihydropyridine: medications affecting the heart and blood vessels (heart and arterioles, ex. diltiazem)
-dihydropyridine: medications affecting mainly blood vessels

name the therapeutic uses of calcium channel blockers (diltiazem)

-angina pectoris
-essential hypertension
-cardiac dysrhythmias

describe the mechanism of action of calcium channel blockers (diltiazem)

-prevent calcium from entering the cells of the heart and arteries (blood vessels relax and open)
-some calcium channel blockers can also slow the heart rate, which can further lower BP (may be prescribed to relieve chest pain (angina) and control an irregular HR)

describe the pharmacokinetics of calcium channel blockers (diltiazem)

-administered orally or IV
-only 20% of oral dose reaches systemic circulation
-elimination is per hepatic metabolism

name the adverse effects of calcium channel blockers (diltiazem)

-constipation
-dizziness
-facial flushing
-headache
-edema of the ankles and feet
-bradycardia
-use with extreme caution with HF patients