Pharmacology Exam 1

Agents normally produced within the body that are used therapeutically

Agents not normally produced within the body (such as foreign chemicals)

• Pharmacology: The study of how drugs affect biological systems
• Therapeutics: The treatment of disease

1906

1914

• 1938
• Durham-Humphrey made legend drugs, which cannot be dispensed without a prescription, and OTC drugs in 1951
• Kefauver-Harris amendments in 1962

• 1970
• Schedule I: Drugs without legal medial use
• II: Drugs with highest abuse potential
• III-V: Decreasing abuse potential

• Preclinical studies
• Clinical studies
• Phase I: Initial dose range and safety
• Phase II: Efficacy in disease and effective dose
• Phase III: Compare with best treatment
• Phase IV: Post-marketing monitoring of new drugs

• Category I: Safe and effective
• Category II: Not safe, not effective, or both
• Category III: Inconclusive data

• 1994
• FDA doesn't regulate vitamins, minerals, herbals, botanicals, amino acids and metabolites, extracts and constituents

• Administration
• Pharmaceutical phase: Disintegration of dosage
• Pharmacokinetic phase: Absorption, distribution; metabolism and excretion is also included
• Pharmacodynamic phase: Drug-receptor Interation and effect

• Enteral: Oral, sublingual, rectal
• Parenteral: subQ, im, iv, ia, intraspinal
• Pulmonary: Inhilation
• Dermal: Topical and transdermal

50%

• Acids
• pH = pKa + log([ionized]/[non-ionized])
• Ka = [H+][A-]/[HA]
• Bases
• pH = pKa + log([ionized]/[non-ionized])

The non-ionized, more lipid-soluble form crosses biomembranes much more readily than does the ionized, more water-soluble form

• Via active transport through:
• ABC transporters (contain ATPase) that are generally efflux transporters or
• Solute-carrier (SLC) transporters (have an indirect energy source of the chemical gradients) that are generally influx transporters

• Blood flow (differs for tissues)
• Ease of drug crossing membrane barriers (includes effects from pKa of drug, pH of compartments, and concentration gradients)
• Polarity of drug (non-polar drugs go to brain and adipose tissue)
• Binding to plasma proteins

Drugs that are highly bound to plasma proteins may displace one another from binding sites, resulting in greater biologic effects, metabolism, and toxicity

• It is made of tight junctions between endothelial cells, resulting in greater permeability to lipid-soluble drugs than water-soluble ones
• It is NOT fully developed at birth

• Quantal: Arrhythmias, convulsions, death
• Graded: Blood pressure, plasma glucose

• Efficacy: Change in the maximal effectiveness (Emax)
• Potency: Change in the effective dose (ED50); need more drug to get the same response
• A potency ratio can be obtained by dividing effective doses for different drugs. Tells us this drug is __x's more potent than this drug

• A ratio of two doses, the toxic or lethal dose 50 and the effective dose 50
• Tells us how far apart the response curves are, and how safe the drug is

A drug that, by itself, produces a response

A drug that, by itself, produces no response but prevents the agonist response by interacting with the receptor

Any drug that produces a response less than a full maximal efficacy

A drug that, by itself, produces a response to suppress endogenous agonists

• Pharmacological Antagonists
• Competitive: Bind at the same site on the receptor; effects can be overcome by giving more agonist (no change in maximal effectiveness, but ED50 changes)
• Noncompetitive: Effects cannot be overcome because binding is irreversible (there is a change in maximal effectiveness, but no change in ED50)
• Partial agonists: Can be antagonists when given with an agonist; this is because it is decreasing the full agonist activity due to competition for receptor binding
• Chemical Antagonists
• Physiological Antagonists

• Specific: Interacts with only one receptor subtype
• Selective: interacts with several receptor subtypes but has a preference for one of them

Unusual or atypical response in a small percent of individuals

A decreased response that takes hours to develop

Decreased response that develops in minutes

Decreased response or no response

• Side: Minor, undesired
• Adverse: Major, serious medical consequences
• Toxic: Very serious adverse effects

• Chemical properties of the drug
• Drug that interacts with multiple receptor types (dirty drugs)
• Drug that interacts with single receptor type but multiple subtypes of that receptor
• Drug that interacts with single receptor subtype but receptor is in multiple tissues or acts vial multiple receptors

• 1: Redistribution
• 2: Biotransformation
• Phase 1 - Drug becomes more polar due to addition or unmasking of an -OH, -NH2, or -SH. Oxidations (P450s, CYPs, or monoamine oxidases), reductions (oxidoreductases), and hydrolysis (cholinesterases) are included
• Phase 2 - Drug becomes conjugated and very polar by addition of an endogenous polar substance such as glucuronic acid, sulfate, an amino acid, or GSH (transferases)
• 3: Excretion

R-H + O2 + NADPH ----> R-OH + H2O + NADP

• They are all transferases
• Glucuronyl Transferases (UGTs 1, 2, or 8): First, substrate is activated to make UDPGA, and then a GA is transferred to the R group and leaves UDP
• Sulfotransferases (ST 1 or 2): Also happens in two steps, annd makes a sulfate (SO4) added onto R group from PAPS
• Catechol-O-methyltransferase (COMT)
• Acetyltransferases
• Glutathione transferases

A drug metabolite that has significant activity (sometimes greater than the parent compound)

Inactive or relatively inactive precursor that is converted by metabolism to a more active compound

Very toxic compound produced by biotransformation of a relatively inert substance

• Cimetidine (an imidazole), erythromycin (an antibiotic), grapefruit (part of the bioflavonoids), an proadifen (SKF 525-A) all decrease metabolism and increase drug levels
• Different CYPs are inhibited, usually directly
• Common site of drug-drug interaction

• Ethanol, phenobarbital, phenytoin, and DDT all activate metabolism and decrease drug levels
• Different CYPs are affected to enhance synthesis, reduce degradation, or directly activate enzymes
• Common site of drug-drug interaction

• Major: Kidney, liver, GI tract, lungs
• Minor: Mammary gland, tears, saliva, sweat

Increased plasma concentration and enhanced drug effects!

• Filtration
• Kidney glomerulus
• Liver when under 200MW
• Passive Diffusion
• Kidney
• Active Secretion
• Proximal tubules of kidney by organic anion/cation transporters, MRPs, P-glycoproteins, or conjugates
• Liver also has OATs/OCTs, MRPs, and transporters for bile salts and steroids
• OATs are inhibited by probenecid and OCTs are inhibited by cimetidine

The average steady-state plasma concentration of a drug that we desire. It's right smack in the therapeutic range

• The fraction of the administered drug reaching the systemic circulation in its active form
• On a graph of drug concentration and time, bioavailability is the area under the curve

• The apparent volume in which a drug distributes. It's a proportionality factor, not a real value.
• = Amount of drug in body / Concentration in plasma
• To determine the plasma concentration at time zero, plot multiple over time as a log and extrapolate Cp

• Removal of drug from a volume of plasma in a given time
• = Rate of elimination / C_p
• = Clearance volumes add up for all systems (renal, liver) and include elimination by excretion and metabolism

• 1st Order Elimination: Delivery-limited; rate of elimination depends on plasma concentration; clearance is constant; a fixed percentage of drug is removed per unit time
• Oth Order Elimination: Capacity-limited; rate of elimination is independent of plasma concentration; clearance is variable; a fixed amount of drug is removed per unit time; when concentration gets really low, 1st order occurs

• CL_organ = Q x ER / dt
• Q: Blood flow
• ER: Extraction ratio
• Extraction ratio = C_i (entering) - C_o (exiting) / C_i

• = C_ss X V_d / F
• The steady-state plasma concentration times the volume of distribution over the fraction of the administered drug reaching the systemic circulation in its active form

• = C_ss x CL x dosing interval / F
• Dependent upon rate of elimination (C_p x CL)

• Dependent on clearance and thus, drug half-life (t_1/2)
• t_1/2 = 0.693 x V_d / CL
• Half-life is a good interval to use initially and then alter after 4-5 doses (plateau effect)

• It increases, because the "first-pass" effect is lessened due to the hepatic disease
• We also need to remember that plasma proteins are decreased

CN III, VII, IX, X and S2-4

T1-12 and L1-3

The preganglionics for both sympathetic and parasympathetic nerves and somatic motor nerves to skeletal muscles

• Acetylcholine: All parasympathetics, all somatic nerves, all preganglionic sympathetic nerves, and some postganglionic sympathetic nerves (about half of them to sweat glands--the thermoregulatory ones)
• Norepinephrine: Most postganglionic sympathetic nerves (non-thermoregulatory sweat glands also)
• Epinephrine: Released by the adrenal medulla directly into the bloodstream
• Dopamine: Some postganglionic sympathetic nerves (smooth muscles of renal and splanchnic vasculature)

• Packaged with primary transmitters and are released into the synapse
• My be a primary NT in noncholinergic/nonadrenergic nerves
• Ex: purines (adenosine, ATP), peptides (cholecystokinin, somatostatin, substance P, neuropeptide Y, vasoactive intestinal peptide), or nitric oxide

• Two cholinergic receptor subclasses
• Nicotinic (ligand-gated ion channels)
• N1: Sympathetic and parasympathetic ganglia
• N2: Neuromuscular junction (somatic nervous system)
• Muscarinic (G protein-coupled receptors) - Mimic the parasympathetic nervous system
• M1: Ganglia and secretory glands
• M2: Smooth muscle and cardiac muscle
• M3 and M4: Smooth muscle, secretory glands, and endothelium

• 7-transmembrane receptors coupled to G proteins
• M1 receptors: Bind G_q/11, and when activated, cause activation of phospholipase C, DAG, and IP3
• M2 receptors: Bind G_i/0, and cause inhibition of cAMP production and K⁺ channel activation
• M3 receptors: Just like M1

• Eye
• Sphincter muscle: Contraction
• Ciliary muscle: Contraction
• Heart (Decreased blood pressure!)
• SA node: Decreased heart rate
• Atria: Decreased contractile strength, decreased refractory period
• AV node: Decrease conduction velocity, increased refractory period
• Ventricles: Small decrease in contractile strength
• Blood Vessels: Dilation via EDRF of both arteries and veins; constriction occurs when a high dose is directly applied
• Lung
• Bronchial muscle: Contraction
• Bronchial glands: Stimulation
• GI Tract: Increases motility, relaxes sphincters, and stimulates secretions
• Urinary Bladder: Contraction of detrusor muscle; relaxation of trigone and sphincter
• Glands: Secretion from sweat glands, salivary glands, lacrimal glans, and nasopharyngeal glands

• Decreased blood pressure
• Constriction of bronchi

Found throughout the body (plasma, liver, glial cells, satellite cells) to break down released ACh by hydrolysis

• Adrenergic receptors (which are all G protein-coupled receptors) at sites innervated by postganglionic sympathetic nerves
• 1: Smooth muscle (activation of phospholipase C)
• 2: Postganglionic sympathetic nerve terminals and presynaptic adrenergic nerve terminals (inactivation of adenylate cyclase)
• 1: Cardiac muscle and presynaptic adrenergic and cholinergic nerve terminals (activation of adenylate cyclase)
• 2: Smooth muscle, cardiac muscle, adipose tissue (activation of adenylate cyclase)

Dopamine receptors on some postganglionic sympathetic nerve terminals and at postjunctional sites on renal vascular smooth muscle

• The stress-responding sweat glands (non-thermoregulatory) are innervated by sympathetics, but about half of these nerves release ACh instead of NE
• "Cholinergic sympathetic" nerves are the ones that release ACh, and it acts upon muscarinic receptors (those are parasympathetic-like)

• By sympathetic nerves which have no postganglionic fibers, and therefore use ACh as the neurotransmitter, just as all other preganglionic sympathetics do
• The chromaffin cells release epinephrine (80%) and norepinephrine (20%) into the venous circulation

Blood vessels, liver, spleen, adrenal medulla, and sweat glands

The parasymphathetic nervous system via muscarinic receptors

• Occurs in the nerve terminal, and is limited by the rate of choline uptake
• Choline uptake occurs via sodium-dependent choline high affinity transport (CHT)
• Choline acetyltransferase (ChAT) makes ACh on the surface of vesicles, which is then transported into synaptic vesicles

• It is hydrolyzed at the ester linkage by acetylcholinesterase in a 2-step reaction, with acetylated AChE as a transient intermediate
• About 50% of the remaining choline molecules are taken up by the CHT mechanism and the rest diffuse away

• 1: Directly stimulating the muscarinic receptors [acetylcholine, bethanechol, carbachol, methacholine, pilocarpine]
• 2A: Inhibiting acetylcholinesterase competitively [edrophonium, tacrine, donepezil demecarium, neostigmine, physostigmine, pyridostigmine]
• 2B: Inhibiting acetylcholinesterase noncompetitively [organophosphate derivatives such as insecticides and nerve gases, malathion, parathion, sarin, soman]. These are irreversible and are highly toxic! Only echothiphate is used clinically for glaucoma. May be reversed with pralidoxime

• Excessive parasympathetic stimulation
• SLUD: Salivation, lacrimation, urination, defecation
• Depressed heart rate and arterial pressure

• Atropine may be given to antagonize muscarinic receptors
• Norepinephrine may be given to activate adrenergic receptors, since we want to decrease parasympathetic activity and increase sympathetic
• Pralidoxime can be given to reactivate AChE (before it has reached the "aged" stage)

• Peripheral: Mydriasis (to dilate the pupil); cycloplegia (to lose accomodation of the lens); to decrease secretions of the respiratory tract before giving inhalant anesthetics; to calm hyperactive smooth muscle, GI, or genitourinary incontinence; when patient has excess bradycardia and hypotension (can be from cardiac catheterization, excessive vagal activity, muscarinic drugs, and inhibitors of AChE), poisoning with organo-phosphates, poisoning with muscarine-containing mushrooms; or as preanesthetic medications to ellicit amnesia (can be given for amnesia post-operatively also)
• Central: Anti-Parkinson, anti-motion sickness, induction of amnesia prior to surgery

• Non-quaternary amines will cross the BBB, causing therapeutic actions or side effects
• Tertiary amines are also good at crossing mucous membranes and for topical use in the eye

• Peripheral: Photophobia (mydriasis/dilation), cycloplegia, xerostomia (dry mouth), tachycardia, difficult urination, red skin ("atropine flush"), increase in skin temperature, decreased sweating
• Central: Sedation or excitement, amnesia

• Muscarinic receptors or nicotinic
• We only use antimuscarinics clinically, since antinicotinics would block parasympathetic and sympathetic ganglia and skeletal muscle

• Increased heart rate
• Increased blood pressure
• Inhibition of GI movements
• Failure to empty bladder and rectum
• Inhibition of mucosal cells and salivary/lacrimal glands
• Dilation of bronchi

• Muscarinic antagonists competitively bind muscarinic receptors
• However, at high dosages, a partial blockage of autonomic ganglia occurs, even though they are nicotinic receptors

• Atropine blocks muscarinic receptors, thereby blocking the "cholinergic sympathetic" sweat glands, which are thermogenic
• This results in an increased body temperature due to impaired ability to sweat

• In Parkinson disease, excess cholinergic activity results in tremor and rigidity
• This occurs due to a loss of dopamine-producing cells
• Treat with levodopa (dopamine precursor) and anticholinergic drugs that are tertiary amines

• Tertiary: Can cross BBB and mucous membranes; good for use in the eye
• Quaternary: Cannot cross BBB due to poor lipid solubility from charged ammonium group; very bad absorption following oral administration; also poorly absorbed across the conjunctiva

• Ganglionic stimulants: Amplify stimulation of both sympathetic and parasympathetic divisions of the ANS by stimulating N1 receptors
• Ganglionic blockers: Inhibit neurotransmission by N1 receptors with equal potency and efficacy in both sympathetic and parasympathetic ganglia; such a broad effect, are difficult to use clinically
• Clinical uses: Adjunct therapy for severe hypertension and severe peripheral vascular disease

• Nicotine causes: Increased cardiac rate, vasoconstriction, and plasma levels of epinephrine from stimulation of adrenal medulla; decreased mucociliary movement in lungs; and mild CNS stimulation
• Also causes small cell carcinoma of the lung and cardiovascular disease
• Lethal dose: 40mg (same as cigar), but bioavailability is very low
• Keep in mind that nicotine also stimulates N2 receptors in addition to N1
• Chronic nicotine toxicity from smoking is the largest single preventable cause of illness and premature death (4/5 leading causes of death)

• Used for increasing blood flow to peripheral organs, increasing nutrient absorption from GI tract due to decreased motility, or for decreasing blood pressure to lessen bleeding
• Blocks adrenergic control of blood vessels, resulting in dilation and decreased blood pressure
• Side effects from blocking sympathetics: Postural hypotension, tachycardia, decreased cardiac output, decreased total peripheral resistance, fainting, no sweating (both non- and thermoregulatory sweat glands controlled by sympathetics)
• Side effects from blocking parasympathetics: Dry mouth, urinary retention and constipation, mydriasis and cyclopegia, prevention of erection and ejaculation, and decreased GI motility/secretions

• Denervation supersensitivity: The threshold dose of ACh needed to trigger a response is significantly reduced, due to increased N2 receptor expression on the muscle surface in a disorganized pattern
• Skeletal: Muscle atrophy
• Smooth: Muscles do not atrophy

• Competitive inhibitors of acetylcholine: Drugs that compete with acetylcholine for N2 receptor sites
• These are reversed by use of AChE inhibitors
• Noncompetitive depolarizing agents: These drugs depolarize the end-plate region; cause contraction first, followed by persistent relaxation and inhibition
• These are augmented by use of AChE inhibitors (they are susceptible to breakdown by AChE)

• Competitive inhibitors of acetylcholine: Cause total flaccid paralysis by the fine motor function loss first, followed by limb/neck/trunk muscle function, and finally by loss of intercostal muscles and diaphragm contraction
• Noncompetitive depolarizing N2 inhibitors result in:
• Phase I block: Results in flaccid paralysis due to inability to repolarize; AChE inhibitors augment this effect
• Phase II block: Desensitizing block, because repolarization occurs, but the membrane is resistant to any further depolarization

• Excessive loss of K+ ions from skeletal muscle that can lead to cardiac arrest (CHF patients, burns, trauma)
• Contraction of extra-ocular muscles that could cause eye damage in glaucoma patients
• May produce prolonged Phase II (desensitizing) inhibition of neuromuscular transmission for many hours [maybe due to plasma cholinesterase inhibition by O-P and continued action of succinylcholine or due to a genetic defect in plasma cholinesterase]
• Contraindications: Liver/renal dysfunction; hypotension may occur due to blockage of N1 receptors or histamine release; antibiotics may potentiate blocking; patients with myasthenia gravis; patients with decreased AChE

• Relaxation of skeletal muscle for surgery, intubation, control of ventilation, or treatment of convulsions
• Prevention of broken bones during electroshock therapy
• Relaxation of spastic muscles (rare)
• Remember to: Check respiration

• Transmission can be increased by inhibiting acetylcholinesterase [neostigmine]
• Ephedrine also enhances muscle contraction, but its mechanism is unknown

• A test for genetic variations of the AChE gene
• These patients may respond to succinylcholine with an even longer neuromuscularblockade

• Location and Role: Contraction/constriction of arteries & veins, iris radiator muscle (to cause mydriasis), ejaculation, piloerection; glycogenolysis (liver); and relaxation of GI smooth muscles
• Receptor Mechanism: G protein-coupled; agonists bind G_q; results in activation of phospholipase C
• Major Stimulants: Phenylephrine, methoxmine
• Epinephrine and Norepinephrine: Agonists
• Dopamine:
• Remember big picture - Found at postganglionic sympathetics

• Location and Role: Postganglionic sympathetic nerve terminals; presynaptic adrenergic nerve terminals to allow for negative feedback to decrease NE release from terminals
• Receptor Mechanism: G protein-coupled; agonists binds G_i; results in inhibition of adenylate cyclase
• Major Stimulants: Clonidine, methyl-NE
• Epinephrine and Norepinephrine: Agonists
• Dopamine:
• Remember big picture - Found on postganglionic sympathetic terminals

• Location and Role: Heart and adipose tissue; results in increased heart rate, contractile force, cardiac output, and lipolysis; also found at presynaptic adrenergic and cholinergic nerve terminals
• Receptor Mechanism: G protein-coupled; agonists bind G_s; results in activation of adenylate cyclase
• Major Stimulants: Dobutamine, isoproterenol
• Less-strong stimulants include albuterol, terbutaline, metaproterenol
• Epinephrine and Norepinephrine: Agonists
• Remember big picture - Found at postganglionic sympathetics

• Location and Role: Vasodilation of skeletal muscle; relaxation of myometrium and intestines; dilation of bronchioles; reducing intraocular pressure
• Receptor Mechanism: G protein-coupled; agonists bind G_s; results in activation of adenylate cyclase
• Major Stimulants: Isoproterenol, albuterol, terbulatine, metaproterenol
• Less-strong stimulants include Dobutamine
• Epinephrine and Norepinephrine: Agonists
• Remember big picture - Found at postganglionic sympathetics

Location and Role: Increased glycogenolysis in liver and skeletal muscle

• Location and Role: Renal and mesenteric vasodilation
• Receptor Mechanism: G protein-coupled; agonists bind G_s; result in activation of adenylate cyclase
• Major Stimulants: Fenoldopam
• Dopamine: Agonist
• Remember big picture - Found at postganglionic sympathetics

• Location and Role: Presynaptic nerve terminals; allow for negative feedback to decrease neurotransmitter release
• Receptor Mechanism: G protein-coupled; agonists bind G_i; results in inhibition of adenylate cyclase
• Major Stimulants:
• Less-strong stimulants: Fenoldopam (has a higher affinity for D1)

• Tyrosine made into DOPA by tyrosine hydroxylase
• DOPA to dopamine
• Dopamine to norepinephrine
• Norepinephrine to epinephrine (in adrenal medulla)
• The rate is controlled by neuronal firing frequency: The higher the frequency, the more NT made

• COMT: Transfers a methyl group onto catecholamine
• MAO: Deaminates catecholimine
• These enzymes render catecholamines inactive, and can do their reactions in either order
• Methoxyhydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA) are metabolic products

• Natural: Norepinephrine, Epinephrine, and Dopamine
• Substitutions to Amino Group
• Have greater beta activity
• Isoproterenol
• Dobutamine (slightly greater affinity to B1)
• Terbutaline (greater affinity to B2)
• Substitutions to Benzene Ring
• Decreased potency with longer duration of action (since COMT cannot metabolize efficiently)
• Metaraminol
• Phenylephrine (slightly greater affinity to A1, then A2>>>>B)
• Ephedrine
• Substitutions to Alpha Carbon
• Block oxidation by MAO and have prolonged activity
• Also are able to displace NE from adrenergic storage vesicles
• Metaraminol
• Ephedrine

• Reuptake system for norepinephrine found at the terminal of postganglionic sympathetics
• Amine I transports about half of norepinephrine back into nerve terminal for reuse (rest is diffused or metabolized by MAO or COMT)
• Repackaged into vesicles via vesicular monoamine transporter (VMAT)
• When this is inhibited [cocaine and tricyclic antidepressants], synaptic norepinephrine levels rise, resulting in sympathetic effects

• When these receptors, found on terminal of postganglionic sympathetics, are blocked, sympathetics are stimulated
• This is because A2 and D2 receptors are activated by norepinephrine and dopamine, respectively, and turn off norepinephrine release
• By blocking them, we get greater amounts of norepinephrine in the synapse and a greater sympathetic response
• D2 blockers are antipsychotic agents [haloperidol, chlorpromazine]

• Taken up by amine I (NET) transporter
• Phenylethylamine derivatives: Dopamine, tyramine, ephedrine, amphetamine

• Tumor of the adrenal gland
• Characterized by very elevated relase of epinephrine (and norepinephrine) into venous circulation and catecholamine excess excreted into the urine
• Symptoms: Severe tachycardia, hypertension, headaches, increased sweating (due to nonthermoregulatory apocrine sweat glands)

• Hyptertension can be treated by blocking the sympathetic nervous system
• Presynaptic Nerve Terminal
• Stimulation of A2 [clonidine, guanabenz, a-methyldopa; ] or D2 receptors results in decreased norepinephrine release
• Stabilization of the nerve terminal membrane interferes with norepinephrine release
• Inhibiting synthesis, storage, or release of norepinephrine
• "False" neurotransmitters
• Postsynaptic Receptors
• Blocking A1, B1 (and B2 if nonselective), or D1 receptors

• Include guanabenz, clonidine, and a-methyldopa
• Cause inhibition of norepinephrine release, and thereby inhibit the sympathetic nervous system
• Used to treat hypertension
• Side Effects: Sedation, xerostomia, anorexia, fluid retention, vivid dreams, & CNS stimulation

• Includes bromocriptine
• Causes inhibition of norepinephrine release, and thereby inhibits the sympathetic nervous system
• Used as anti-Parkinson agent (targets post-synapted D2 receptors in CNS)
• Side Effects: Postural hypotension, development of cardiac arrhythmia

• Prevent transport of norepinephrine, epinephrine, serotonin, and dopamine into storage vesicles by VMAT
• Side Effects: Sedation, depression, Parkinsonian symptoms, increased GI motility & ulcers

• Used to lower MAP by inhibiting constriction/contraction, resulting in vasodilation
• Competitive: Prazosin, phentolamine
• Noncompetitive: Phenoxybenzamine

• Most are pure antagonists
• Used for hypertension therapy, often with diuretics and other agents
• B1/B2 Blockers: B2 blockade may inhibit dilation of bronchioles, which may be significant for patients with asthma; they also lower intraocular pressure following corneal application [propranolol, pindolol, timolol, nadolol]
• Selective B1 Inhibitors: Effective hypotension agents; less prone to induce constriction of bronchial smooth muscle in patients with asthma [betaxolol, atenolol, metoprolol]
• Adverse Effects: Must be used with great caution in patients with cardiac insufficiency

• Pheochromocytoma
• Hypertension
• Ischemic heart disease
• Glaucoma to lower intraocular pressure by reducing production of aqueous humor
• Urinary obstruction, such as BPH