Pharmacology - Exam 1 - Road Map 1

Front 1

Formula for calculating bioavailability (F)?

Back 1

F=AUC(route)/AUC(IV)

Front 2

The elimination of drugs that follow first-order kinetics can be characterized by a proportionately constant. What is it called, and what is it defined as?

Back 2

Clearance, Cl. Clearance is defined as: Cl=rate of elimination/plasma concentration

Front 3

Elimination half-life can be derived from graphs of plasma concentration versus time, or it can be obtained by a calculation. Formula of the calculation is?

Back 3

t1/2=(0.693*Vd)/Cl ; Note: ln(2)=0.693

Front 4

The loading dose must fill the volume of distribution of the drug (Vd) to achieve the target plasma concentration (Cp). The formula is

Back 4

Loading dose=(Vd*Cp)/F

Front 5

Maintenance dosage must replace the drug that is being eliminated by the body over time to maintain a steady Cp, and thus it involves Cl. The formula for maintenance dosage is:

Back 5

Maintenance dosage=(Cl*Cp)/F

Front 6

Drug receptors can be divided into five groups. What are the groups, and give some examples of each group

Back 6

1. Steroid: Estrogen, corticosteroids, thyroid hormone
2. Ion channel: Acetylcholine (on nicotinic AChR)
3. Transmembrane tyrosine kinase: Insulin
4. JAK-STAT: Cytokines
5.GPCR: Norepinephrine, ACh (on muscarinic receptors)

Front 7

In the US, scheduled drugs are drugs that are considered to have significant potential for illicit use. They are ranked according to their perceived social danger. The different ranks are

Back 7

I - Banned from prescription or anything other than research use
II - Strongly addicting drugs that nevertheless have important medical uses
III, IV and V - Progressively less addicting

Front 8

In the sympathetic nervous system, the neurotrannsmitter at post-ganglionic nerve endings varies depending on the tissue being innervated. The neurotransmitters used are ACh and Norepinephrine. Give some examples where they are used

Back 8

1. ACh is used for the adrenal medulla, thermoregulatory sweat glands and some vasodilator fibers going to skeletal muscle blood vessels
2. For everything else, there's norepinephrine

Front 9

A drug that can inhibit hydroxylation of tyrosine in the production of norepinephrine

Back 9

metyrosine

Front 10

Monoamine oxidases (MAOs) are present where?

Back 10

On the mitochondria in nerve endings

Front 11

Why aren't NE-synthesizing neurons inhibited by botulin toxin?

Back 11

They lack the endocytoic mechanism for taking up botulin toxin, and so they are not inhibited by botulin toxin

Front 12

Drug that blocks the reuptake of choline in nerve endings? (3)

Back 12

1. hemicholinium-3, or hemicholine
2. blocks the high-affinity transporter ChT; this is the rate-limiting step in ACh synthesis
3. classified as an indirect acetylcholine antagonist

Front 13

Drug that blocks the uptake of ACh.

Back 13

1. vesamicol
2. it is an experimental drug, and it blocks the uptake of ACh into storage vesicles
3. classified as a physiological cholinergic antagonist.

Front 14

Give a few examples of drugs working on presynaptic, noradrenergic nerve endings (4 [5])

Back 14

1. metyrosine - inhibits Tyrosine Hydroxylase; decreases catecholamine synthesis
2. reserpine - blocks vesicular monoamine transporter (VMAT); uptake of dopamine into storage vesicles.
3. guanethidine - competes with norepinephrine uptake into storage vesicles, depleting the nerve ending of NE. In addition it blocks the relase of neurotransmitters in response to an action potential
4. TCA and cocaine - block the Uptake 1 transporter

Front 15

G protein associated with, effect and second messenger of nicotinic receptors

Back 15

1. none
2. opens Na-K-channel
3. depolzarizes cell

Front 16

G protein associated with, effect and second messenger of muscarinic receptors.

Back 16

1. Gq (smooth muscle, some glands [M1, M3, M5]), Gi (cardiac muscle [M2, M4]).
2. Increases IP3 and DAG (Gq), decreases cAMP & opens K+ channels (Gi)

Front 17

G protein associated with, effect and second messenger of α1-receptors.

Back 17

1. Gq (smooth muscle, some glands)
2. Increases IP3 and DAG

Front 18

G protein associated with, effect and second messenger of α2-receptors

Back 18

1. Gi (smooth muscle, preganglionic nerve endings, CNS)
2. Decreases cAMP

Front 19

G protein associated with, effect and second messenger of β1, β2, β3 receptors

Back 19

1. Gs (smooth and cardiac muscle, juxtaglomerular apparatus, adipocytes)
2. Increases cAMP.

Front 20

Effect of sympathetic discharge (and receptor type) on eye

Back 20

dilates pupil (α)

Front 21

Effect of sympathetic discharge (and receptor type) on airways

Back 21

dilates bronchioles (β2)

Front 22

Effect of sympathetic discharge (and receptor type) on GI tract

Back 22

slows motility (α, β2)

Front 23

Effect of sympathetic discharge (and receptor type) on GU tract

Back 23

1. contracts prostate and bladder sphincters (α)
2. mediates ejaculation (α)

Front 24

Effect of sympathetic discharge (and receptor type) on vessels (2)

Back 24

1. constricts arterioles in skin and splanhcnic vessels (α)
2. dilates skeletal muscle vessels (β2)

Front 25

Effect of sympathetic discharge (and receptor type) on heart

Back 25

1. accelerates all pacemaker and AV conduction (β1, β2)
2. increases force of contraction (β1, β2)

Front 26

Effect of sympathetic discharge (and receptor type) on exocrine glands (2)

Back 26

1. increases sweating (M)
2. salivation (slight, α)

Front 27

Effect of sympathetic discharge (and receptor type) on metabolism (5)

Back 27

Increases:

1. glycogenolysis (β)
2. free fatty acids in blood (β)
3. renin release (β)
4. potassium release and uptake (β)
5. potentiates thyroid effects (β)

Front 28

Effect of sympathetic discharge (and receptor type) on skeletal muscle

Back 28

1. increases strength (α)
2. causes tremor (β2)

Front 29

Effect of parasympathetic discharge (and receptor type) on eye (2)

Back 29

1. Constricts pupil (miosis) (M)
2. Focuses for near vision (M)

Front 30

Effect of parasympathetic discharge (and receptor type) on airways

Back 30

constricts bronchioles (M)

Front 31

Effect of parasympathetic discharge (and receptor type) on GI tract

Back 31

increases motility and secretion (M)

Front 32

Effect of parasympathetic discharge (and receptor type) on GU tract

Back 32

1. contracts wall of bladder (M)
2. mediates erection (M)

Front 33

Effect of parasympathetic discharge (and receptor type) on vessels

Back 33

little effect

Front 34

Effect of parasympathetic discharge (and receptor type) on heart (2)

Back 34

1. slows sinus rate and AV conduction (M)
2. increases AV refractory period (M)

Front 35

Effect of parasympathetic discharge (and receptor type) on exocrine glands

Back 35

1. increases salivation markedly (M)
2. increases lacrimal secretion (M)
3. increases gastric secretion (M)
4. increases duodenal secretion (M)
5. increases pancreatic secretion (M)

Front 36

Effect of parasympathetic discharge (and receptor type) on metabolism

Back 36

little effect

Front 37

Effect of parasympathetic discharge (and receptor type) on skeletal muscle

Back 37

little effect

Front 38

Clinical uses of cholinomimetics (6)

Back 38

1. Treatment of Glaucoma (constrict, reduce intraocular pressure by increasing outflow of aqueous humor)
2. Reduce systemic toxicity (pilocarpine and physostigmine)
3. Treatment of ileus (bethanechol or neostigmine orally or subcutaneously)
4. Treatment of urinary retention
5. Myasthenia gravis (direct-acting cholinomimetics are useless here)
6. Insecticides

Front 39

Toxicities of direct-acting and indirect acting cholinomimetics are similar, but because cholinesterase inhibitors amplify the nicotinic and the muscarinic actions, more nicotinic manifestations may be observed. These toxicities (of cholinergic overdose) are best remembered with the mnemonic

Back 39

D - diarrhea, defecation (M)
U - urination (M)
M - miosis (muscarinic)
B - bronchospasm (M)
B - bradycardia (M))
E - excitation (of CNS and skeletal muscle receptors)
L - lacrimation (M)
S - salivation (M)
S - sweating (M)

Front 40

Muscarinic receptor blockers are what kind of blockers?

Back 40

They are competitive pharmacologic antagonists, shifting the graded dose-response curve for agonists to the right

Front 41

Nicotinic receptor blockers are what kind of blockers?

Back 41

Include two separate groups of drugs that selectively block ganglia or the neuromuscular junction in skeletal muscle.
1. ganglion blockers are rarely used; neuromuscular blockers are very important in anesthesiology.
2. both categories are competitive pharmacological antagonists.

Front 42

Actions and toxicities of muscarinic blockers on the CNS (5)

Back 42

Therapeutic doses:
1. sedation
2. reduction of motion sickness
3. reduction of Parkinsonian tremor.

Toxic doses:
4. hallucinations
5. convulsions

Front 43

Actions and toxicities of muscarinic blockers on the eyes

Back 43

Marked mydriasis and cycloplegia

Front 44

What is cycloplegia?
What is mydriasis?

Back 44

1. loss of accomodation, due to paralysis of the ciliary muscle
2. excessive dilation of pupil, due to paralysis of the muscles of iris and ciliary body

Front 45

Actions and toxicities of muscarinic blockers on the airways (2)

Back 45

1. little effect on normal airways
2. used to treat bronchospasm in some patients with asthma.

Front 46

Actions and toxicities of muscarinic blockers on the GI tract

Back 46

1. Salivation is markedly reduced by small doses.
2. High therapeutic doses reduce hypermotility and secretion of gastric acid, but other drugs are preferred.

Front 47

Actions and toxicities of muscarinic blockers on the GU tract

Back 47

moderate doses reduce bladder tone and may precipitate urinary retention (esp. in older men)

Front 48

Actions and toxicities of muscarinic blockers on the cardiovascular system (3)

Back 48

at therapeutic doses;

1. no effect on vessels
2. heart rate and AV conduction velocity usually increase due to vagal blockade.
3. High doses: flushing of the skin

Front 49

Toxicities of ganglion blockers (5)

Back 49

1. Cycloplegia
2. Orthostatic hypotension
3. Constipation
4. Urinary retention
5. Sexual dysfunction

Front 50

Modes of action of neuromuscular nicotinic blockers (2)

Back 50

1. competitive pharmacologic antagonism (nondepolarizing blockers)
2. prolonged acetylcholine-like agonist action (depolarizing blockers)

Front 51

Mode of action and indications for nondepolarizing blockers

Back 51

1. Prevent depolarization of the end-plate
2. Used for surgical procedures of medium and long duration

Front 52

Toxicities of nondepolarizing blockers (2)

Back 52

1. hypotension (from histamine release and ganglion blockade)
2. may require respiratory support (if excessive blockade)

Front 53

Six representative antimuscarinic drugs

Back 53

1. atropine
2. scopolamine
3. benzotropine
4. glycopyrrolate
5. ipratropium
6. oxybutynin

Front 54

Properties of atropine (5)

Back 54

1. lipid soluble
2. enters CNS and eye readily
3. duration of action 4-8 hours except eye, >72 hours.
4. reduces airway secretion and AV block
5. causes mydriasis and cycloplegia; an important antidote for cholinomimetic overdose

Front 55

Properties and uses of scopolamine (3)

Back 55

1. similar to atropine
2. strong anti-motion sickness effect
3. causes mydriasis and cycloplegia

Front 56

Properties and uses of benzotropine (3)

Back 56

1. centrally acting anticholinergic/antihistaminic agent
2. enters CNS readily
3. treat parkinsonism

Front 57

Properties and uses of glycopyrrolate (3)

Back 57

1. enters CNS poorly
2. good peripheral muscarinic blockade
3. reduces parasympathetic effects on the GI and GU tracts

Front 58

Properties and uses of ipratropium (4)

Back 58

1. anticholinergic (anti-muscarinic)
2. enters CNS poorly
3. short half-life in blood
4. used by inhalation route for asthma

Front 59

Properties and uses of oxybutynin (2)

Back 59

1. enters CNS but strong peripheral muscarinic blockade
2. reduces bladder urgency and spasms

Front 60

Some representative nicotinic-blocking drugs (4)

Back 60

1. hexamethonium (prototype ganglion blocker)
2. trimethaphan (ganglion blocker)
3. d-Tubocurarine
4. succinylcholine, also known as suxamethonium (depolarizing nicotinic blocker)

Front 61

Properties and uses of hexamethonium (3)

Back 61

1. prototype ganglion blocker
2. no CNS effects
3. no uses (obsolete antihypertensive)

Front 62

Properties and uses of trimethaphan

Back 62

1. very short-acting ganglion blocker, parenteral only
2. used in hypertensive emergencies

Front 63

Properties and uses of d-tubocurarine

Back 63

1. long acting (3-60 minutes) nondepolarizing neuromuscular blocker prototype, histamine releaser and weak ganglion blocker; requires good renal function for elimination
2. produces neuromuscular paralysis for surgery; mechanical ventilation is usually required

Front 64

Properties and uses of succinylcholine (4)

Back 64

1. it is an agonist, also known as suxamethonium
2. depolarizing neuromuscular blocker
3. very short (3-10 minutes) duration of action
4. produces neuromuscular paralysis of very short duration

Front 65

What is pralidoxime? (3)

Back 65

1. cholinesterase regenerator
2. antidote in severe cholinesterase inhibitor poisoning caused by organophosphate insecticides (atropine is also used in all cases of cholinesterase inhibitor poisoning)
3. it is an antagonist, has a high affinity for phosphorous, and frees up the cholinesterase

Front 66

Examples of direct-acting sympathomimetics (4)

Back 66

1. epinephrine
2. norepinephrine
3. dopamine
4. isoproterenol (isoprenaline)

Front 67

Examples of indirect-acting sympathomimetics (4)

Back 67

1. amphetamines (displace transmitter from its stores)
2. ephedrine (displace transmitter from its stores)
3. cocaine (inhibits reuptake)
4. TCAs (inhibit reuptake)

Front 68

Actions of sympathomimetics on the CNS

Back 68

1. indirect-acting agents produce a dose dependent sequence of stimulant effects, ranging from mildly alerting and reduction of fatigue to a definite elevation of mood and insomnia, and to marked anorexia and euphoria
2. probably more related to dopamine release than to NE release

Front 69

Actions of sympathomimetics on eyes

Back 69

α1-activation in the pupillary dilator muscle results in mydriasis

Front 70

Actions of sympathomimetics on airways

Back 70

beta2-activation results in bronchodilation

Front 71

Actions of sympathomimetics on the GI tract

Back 71

both α and β receptors mediate reduced motility

Front 72

Actions of sympathomimetics on the GU tract

Back 72

1. α1 receptors mediate increased sphincter tone in the bladder and prostate
2. β2 receptors mediate uterine relaxation

Front 73

Actions of sympathomimetics on the heart

Back 73

1. β-receptors mediate increased myocardial contractility and increased heart rate
2. the net heart rate effects depend on the reflexes evoked by the changes in blood pressure

Front 74

Other effects of β-receptor activation (3)

Back 74

1. increased blood insulin and FFA levels
2. hyperkalemia, followed by hypokalemia and leukocytosis
3. β2 agonists cause tremor in skeletal muscles at most doses

Front 75

Uses of sympathomimetics (CNS)

Back 75

amphetamines are used to treat
1. ADHD
2. narcolepsy
3. and to decrease appetite

Front 76

Uses of sympathomimetics (pulmonary and cardiac) (3)

Back 76

1. epinephrine is used to treat anaphylactic shock
2. β2 agonists (by inhalation) for acute asthmatic bronchospasm
3. β agonists are occasionally used to increase heart rate

Front 77

Vascular uses of sympathomimetics (3)

Back 77

1. α agonists are used to decrease blood flow (to reduce bleeding and congestion and to prolong local anesthesia)
2. dopamine is used to maintain renal blood flow in shock
3. midodrine is used to treat idiopathic orthostatic hypotension

Front 78

Genitourinal (GU) tract uses of sympathomimetics

Back 78

1. α-agonists: reduce urinary incontinence; long-acting indirect oral agents (e.g., ephedrine) are suitable
2. β2 agonists, e.g., ritodrine and terbutaline, are sometimes used to suppress preterm labour (but their value is controversial)

Front 79

Toxicities of sympathomimetics (4)

Back 79

1. arrhythmias (all)
2. myocardial infarction (all)
3. amphetamine and cocaine have a high addiction potential, may cause seizures
4. in high systemic concentrations: α-agonists - stroke; high local concentrations - local tissue ischemia and necrosis

Front 80

Give some examples of representative α-blockers

Back 80

1. Prazosin (α1-selective) - competitive pharmacologic antagonist
2. Phentolamine (nonselective) - competitive pharmacologic antagonist
3. Phenoxybenzamine (nonselective) - irreversible in mode of action, thus preferred in pheochromocytomas
4. Tamsulosin - α1-selective (uroselective). prostatic hyperplasia
5. Yohimbine - α2-selective, not clinically used

Front 81

Action of α-blockers

Back 81

1. prevent smooth muscle contraction
2. decreased peripheral resistance and blood pressure, often accompanied by reflex tachycardia
3. in the GU tract, α-receptors mediate contraction of prostate smooth muscle; α-blockers are able to reduce urinary obstruction in men with benign prostatic hyperplasia

Front 82

What is epinephrine reversal phenomenon?

Back 82

In the presence of high concentration of epinephrine, α-blockers cause an actual reversal of of the blood pressure response to the agonist: the normal hypertensive response (elevated blood pressure, mediated by α-receptors) is converted to a hypotensive response (mediated by β2 receptors)

Front 83

Norepinephrine binds to which receptors? (3)

Back 83

1. α1
2. α2
3. β1

Front 84

Epinephrine binds to which receptors?

Back 84

1. α1
2. α2
3. β1
4. β2

Front 85

Isoproterenol binds to which receptors? (2)

Back 85

1. β1
2. β2

Front 86

Dopamine binds to which blood vessel and heart receptors?

Back 86

1. D2
2. beta
2. alpha (high concentrations)

Front 87

Phenylephrine is what kind of agonist?

Back 87

α1-selective agonist

Front 88

Albuterol binds to

Back 88

β2 receptors (also known as salbutamol)

Front 89

Effect on vascular tone, blood pressure and heart rate of norepinephrine

Back 89

1. skin/viscera: ++
2. skeletal muscle: (+)
3. kidneys: (+)
4. blood pressure: +++
5. heart rate: - - (reflex)

Front 90

Effect on vascular tone, blood pressure and heart rate of epinephrine

Back 90

1. skin/viscera: ++
2. skeletal muscle: - -
3. kidneys: (+)
4. blood pressure: ++
5. heart rate: variable

Front 91

Effect on vascular tone, blood pressure and heart rate of isoproterenol

Back 91

1. skin/viscera: none
2. skeletal muscle: - -
3. kidneys: none
4. blood pressure: - -
5. heart rate: +++

Front 92

Effect on vascular tone, blood pressure and heart rate of dopamine

Back 92

1. skin/viscera: none
2. skeletal muscle: none
3. kidneys: - -
4. blood pressure: +
5. heart rate: variable

Front 93

Effect on vascular tone, blood pressure and heart rate of phenylephrine

Back 93

1. skin/viscera: +
2. skeletal muscle: (+)
3. kidneys: +
4. blood pressure: +
5. heart rate: - - (reflex)

Front 94

Effect on vascular tone, blood pressure and heart rate of albuterol

Back 94

Also known as salbutamol. It is a SAB2A

1. skin/viscera: none
2. skeletal muscle: - -
3. kidneys: none
4. blood pressure: -
5. heart rate: +

Front 95

Prototype substances that bind to all α-receptors? (2)

Back 95

1. norepinephrine
2. epinephrine

Front 96

Prototype α1 agonist, and its properties

Back 96

1. midodrine
2. activates Gq; PLC cleaves PIP2, increases IP3, DAG
3. smooth muscle contraction
4. used to treat orthostatic hypotension

Front 97

Prototype α2 agonist, and its properties (4)

Back 97

1. clonidine
2. activates Gi, decreases cAMP
3. inhibits transmitter release
4. mediates smooth muscle contraction

Front 98

Prototype β agonists (2)

Back 98

1. a. isoproterenol (isoprenaline [INN])
b. epinephrine
2. activates Gs, increases cAMP
3. effects vary on the subfamily

Front 99

Prototype β1 agonist

Back 99

1. dobutamine
2. activates Gs, increases cAMP
3. cardiac stimulation
4. increased renin release

Front 100

Prototype β2 agonist

Back 100

1. albuterol (USAN) or salbutamol (INN) (SAB2A)
2. activates Gs, increases cAMP
3. cardiac stimulation
4. smooth muscle relaxation
5. glycogenolysis
6. tremor

Front 101

Prototype β3 agonist, and effects of β3 activation

Back 101

1. -
2. activates Gs, increased cAMP
3. lipolysis

Front 102

Prototype substance that binds to all dopamine receptors

Back 102

dopamine

Front 103

Prototype substance that binds to D1 receptors, and its properties

Back 103

1. fenoldopam
2. activates Gs, increased cAMP
3. vasodilation

Front 104

Prototype substance that binds to D2 receptors and its properties

Back 104

1. -
2. activates Gi, decreases cAMP
3. inhibition of transmitter release

Front 105

Toxicities of α-blockers (3)

Back 105

1. tachycardia as a reflex (nonselective more so than selective α1 blockers)
2. GI upset (phentolamine and phenoxybenzamine)
3. postural hypotensive response (some α1-selective agents)

Front 106

Prototype full antagonist β blocker

Back 106

propranolol (stage fright, familial tremor)

Front 107

Properties of pindolol

Back 107

1. Nonselective β-blocker
2. Partial β-agonist, used as antagonist

Front 108

Prototype β1-selective antagonist

Back 108

atenolol

Front 109

Mechanism of action of carvedilol (2)

Back 109

1. selective α1 antagonist
2. nonselective β antagonist

Front 110

Mechanism of action of labetalol

Back 110

1. selective α1 antagonist
2. nonselective β-antagonist

Front 111

Mechanism of action of esmolol

Back 111

1. parenterally given selective β1 antagonist (antiarrhythmic)
2. half life: 9 mins, 4.5 in <16 yo

Front 112

Define parenteral

Back 112

by other means than the alimentary tract (e.g., IV or intramuscular)

Front 113

CNS effects of beta blockers (2)

Back 113

1. sedation/lethargy
2. reduction of anxiety

Front 114

Effects of β-blockers on the eyes

Back 114

1. reduced secretion and production of aqueous humor
2. reduced ocular pressure
3. no significant effect on pupil or focus

Front 115

Airway effects of beta blockers

Back 115

marked bronchospasm in patients with airway disease, especially asthma

Front 116

Cardiovascular effects of beta blockers (3)

Back 116

1. slowed heart rate and AV conduction
2. reduced myocardial contractility
3. reduced blood pressure

Front 117

GI and GU tract effects of β-blockers

Back 117

little effect

Front 118

Other effects of β-blockers (4)

Back 118

1. reduced skeletal muscle tremor
2. reduced glucose release from the liver
3. reduced renin release from the kidney
4. reduced thyroid hormone effects

Front 119

Uses of β-blockers (5)

Back 119

1. Treatment of HTN, angina, and arrhythmias
2. Reduce mortality and morbidity after MI or HF
3. Oral β-blockers reduce familial tremor and stage fright
4. Topical β-blockers to treat glaucoma
5. IV and oral β-blockers are useful in treatment of thyrotoxicosis

Front 120

define: mortality

Back 120

death rate: the ratio of deaths in an area to the population of that area; expressed per 1000 per year

Front 121

define: morbidity

Back 121

the symptoms and/or disability resulting from a disease

Front 122

Toxicities of β-blockers (4)

Back 122

1. symptomatic cardiac depression (bradycardia, AV block, diminished cardiac output)
2. elevated blood glucose, lipids, and uric acid (chronic therapy)
3. severe bronchospasm (in asthma patients)
4. symptoms of hypoglycemia are masked (e.g., from an insulin overdose)