Pharm Exam 1 Christian

Front 1

What is the difference between the words affinity and efficacy with relation to receptors/ligands? What is a partial agonist?

Back 1

Affinity is the tendency of a drug to bind to receptors

Efficacy is the tendency for the ligand, once bound, to activate the receptor

Partial agonist is one with intermediate levels of efficacy (therefore submaximal tissue response)

Front 2

Which receptors show an appreciable level of activation even when no ligand is present?

Back 2

Cannabinoids
Benzodiazepines
Serotonin

*Others exist as well*

Front 3

What is the efficacy of each of the following?
1) Inverse agonist
2) Agonist
3) Competitive antagonist

Back 3

1) Negative
2) Positive
3) Zero

Front 4

What is an inverse agonist?

Back 4

One that reduces the level of constitutive activation. ( If drug has a higher affinity for the nonactive state)

Front 5

How does a competitive antagonist work in terms of efficacy?

Back 5

When there is no preference between the active and nonactive form of the receptor

Front 6

What state do most receptors exist in?

Back 6

Inactive. Very few remain in active state.

Front 7

Spare receptors are commonly involved with which types of drugs?

Back 7

Ones that elicits smooth muscle contraction.

Front 8

What is chemical antagonism?

Back 8

It occurs when two substances combine in solution and as a result the effect of the active drug is lost. ( Ex. the use of chelating agents that bind to heavy metals)

Front 9

What is pharmacokinetic antagonism?

Back 9

Occurs when the antagonist effectively reduces the concentration of the active drug at its site of action through affecting its absorption, metabolism, excretion etc.

Front 10

What are the classifications of antagonism by receptor block ?

Back 10

- Reversible (equilibrium) or irreversible (non-equilibrium)
- Reversible is the most commonest and most important type of antagonism

Front 11

What are the two main characteristics of competitive antagonism?

Back 11

1- in the presence of the antagonist, agonist log [ ] - effect curve is shifted to the right with no change in slope or max. (Hallmark!)

2- Dose ratio increases linearly with antagonist concentration (slope of line is affinity)

Front 12

What is important about competitive antagonism that differs from other forms of antagonism?

Back 12

This type of antagonism is said to be surmountable. This means that because the two are in competition, raising the agonist concentration can restore the agonist occupancy

Front 13

What is a dose ratio?

Back 13

It expresses the shift in a log concentration curve and is defined by the ratio of agonist concentration which has to be increased in presence to an antagonist, to restore response

Front 14

What is characteristic of non-competitive antagonism?

Back 14

Reduction in slope and max of agonist log [ ] curve. Generally , it is the situation where the antagonist blocks at some point the chain of events leading to response

Front 15

What is physiological antagonism?

Back 15

A term used loosely to describe the interaction of two drugs whose opposing actions in the body tend to cancel each other

Front 16

What is desensitisation or tachyphylaxis? Tolerance? Drug resistance

Back 16

The effect of a drug gradually diminishes when it is given continuously. (develops in a few minutes)

Tolerance is used to describe a more gradual decrease in responsiveness to a drug (days to weeks to develop)

Drug resistance is used to describe the loss of effectiveness of antimicrobial or antitumor drugs.

Front 17

What occurs during prolonged exposure to agonists?

Back 17

Gradual decrease in number of receptors expressed ( internalisation of receptors)

Front 18

What does the pronounced tolerance to nitrovasodilators result from?

Back 18

Decreased metabolism

(as opposed to ethanol and barbiturates to which tolerance develops to due to increased metabolic degradation)

Front 19

What is physiological adaptation?

Back 19

When a drug's effects are reduced because it is nullified by a homeostatic response

Front 20

Which law does binding of drugs obey?

Back 20

Law of Mass Action

Front 21

Which drugs bind to accessory sites on ion channel proteins, thus affecting channel gating?

Back 21

Dihydropyridine (vasodilator - inhibits opening of L-type Ca Ch.)

Benzodiazepines (bind to region of GABA receptor-chloride channel complex)

Sulfonylureas ( act on ATP-sensitivty potassium channels of pancreatic B-cells - used in treatment of diabetes (^ insulin production)

Front 22

List the types of receptors in order of fastest reaction time to slowest

Back 22

Type 1:Ligand-gated[ionotropic] (ms)
Type 2: G-protein-coupled [metabotropic] (s)
Type 3: Kinase-linked (hrs)
Type 4: Nuclear (hrs)

Front 23

Which receptors constitute the largest family?

Back 23

G-protein

Front 24

What are the families of G-protein receptors?

Back 24

Family A (rhodopsin fam): Largest. Receptors for most things. Short N terminal tail (extracell.)

Family B (secretin/glucagon fam): Receptors for peptide hormones (including secretin, glucagon, calcitonin). Intermediate extracell. tail

Family C. Small. Includes: GABAb receptors, Ca-sensing receptors , metabotropic glu receptors. Long extracellular tail.

Front 25

What are some examples alternative mechanims of receptor activation?

Back 25

1) Rhodopsin being activated by light inducing cis-trans isomerisation of retinal

2) PARs, when activated, bind to receptor domains and act as tethered agonists.

3) Receptor mutations

Front 26

What are the G-protein subtypes and their main effects

Back 26

G(alpha)s - Stimulates adenylyl cyclase (^cAMP)

G(alpha)i - Inhibits adenylyl cyclase (Dec. cAMP)

G(alpha)o - Limited effects of a subunit

G(alpha)q - Activates PLC

G(beta)(gamma) - Same effects as alpha subunits but also other effects.

Front 27

What are characteristics of G protein receptors?

Back 27

- 7 membrane-spanning a-helices
- One intracellular loop is larger than the others which interacts with G proteins
- G-proteins are made up of a,b,y subunits and a subunit has the GTPase activity

Front 28

How are the effects of G proteins turned on and off?

Back 28

Turned on:
- GDP-GTP exchange causing dissociation of G-protein trimer, releasing a and by subunits (active forms)

Turned off:
- GTP is hydrolyzed to GDP through GTPase activity of alpha subunit. a-GDP molecule then dissociates from effector and reunites with By subunit.

Front 29

What is cAMP inactivated by? What are some drugs that inhibit the action of these inhibitors?

Back 29

Phosphodiesterases. They cause hydrolysis to 5'-AMP.

PDE inhibitors:
Caffeine (general)
Rolipram [asthma] (PDE4 selective)
Sildenafil (Viagra) (PDE5 selective)

Front 30

Describe breifly the phosphatidylinositol cycle

Back 30

GPCR activation leads to activation of PLCb which cleaves PIP2 into DAG and IP3. DAG activates protein kinase C and IP3 causes the release of intracellular Ca. DAG is then phosphorylated into phosphatidic acid which combines with inositol (from IP3 recycle) to form PI which is then again phosph. to PIP2. (cycle complete) . IP3 can be converted into IP4 in cells or it can be dephosphorylated into IP by phosphatases and then it is convereted into inositol by Ionsitol 1-phosphatase (this inositol combines with phosphatidic acid)

Front 31

Which plant compounds can cause PKC activation?

Back 31

Phorbol esters

Front 32

On what basis does Lithium work?

Back 32

It inhibits inositol 1-phosphatase which prevents IP3 recycling.

Front 33

What is the Rho/Rho kinase system?

Back 33

It is a pathway which is also activated by GPCRs among others. The free G-alpha unit interacts with guanosine nucleotide exchange factor which forms Rho-GTP (active) from Rho-GDP. This activated Rho kinase which is involved in numerous things. *May be important in pathogenesis of pulmonary hypertension

Front 34

How does GPCR desensitisation occur?

Back 34

By:

Receptor phosphorylation
Receptor internalization

Front 35

What are the types of kinase-linked receptors?

Back 35

- Receptor tyrosine kinase ( receptors for growth factors, and insulin receptor belongs to this class)
- Serine/Thr kinase (ex. TGF receptor)
- Cytokine (lack intrinsic enzymatic activity so, when activated, they activate a cytosolic tyrosine kinase)
- Guanylyl cyclase-linked receptors - example ANF receptor

Front 36

How can supersensitivity occur ?

Back 36

1 - Nerve denervation
2 - Pharmacological block

The end organs become supersensitive to small amounts of transmitter

Front 37

What are heterotropic interactions?

Back 37

When one neurotransmitter affects the release of another for example. Homotropic would be when the transmitter binds to the presynaptic autoreceptors and affects the nerve.

Front 38

How is ACh removed from cholinergic synapses ?

Back 38

Acetylcholinesterase. Most other cases of synapses, there is active reuptake into the presynaptic nerve or into supporting cells

Front 39

Which aspect of synthesis/storage/release of amine/aa transmitters cannot be influenced by drugs?

Back 39

Transmitter diffusion

Front 40

What are the two actions of acetylcholine?

Back 40

Muscarinic and Nicotinic.

Muscarinic actions can be reporduced by injection of muscarine and can be abolished by small doses of atropine. These actions include: vasodilation (via NO) and other parasympathetic actions.

Nictonic receptors provide effects similar to those of nicotine. These include: stimulation of all autonomic ganglia, stimulation of voluntary muscle, secretion of adrenaline from the adrenal medulla.

Front 41

What 3 classes of nictonic ACh receptors are there? General structure?

Back 41

Muscle
Ganglionic
CNS

Pentameric structure functioning as a ligand-gated ion channels. There are two binding sites for ACh (both need to be bound for activation) located at the extracellular domain of each alpha subunit.

Front 42

What are muscarinic receptors? Subtypes?

Back 42

G-protein-coupled receptors. Subtypes: M1-M5.

Odd numbers: 1,3,5 couple with Gq -> inositol phosphate

Even #: 2,4 couple with Gi to inhibit adenylyl cyclase

4 and 5 are mainly in the CNS

Front 43

Where can M1 receptors be found? M2?

Back 43

M1 (neural) = Mainly on CNS and peripheral neurons but also on gastric parietal cells. They mediate excitatory effects (mainly by decreasing K conductance)

M2 (cardiac) = occur in the heart and presynaptic terminals of peripheral and central neurons. They exert inhibitory effects (mainly by increasing K conductance and inhibiting Ca channels)

M3 (smooth m.) are found in glandular/smooth muscle and produces mainly excitatory effects (i.e secretions and contraction of visceral smooth muscle). M3 can also cause relaxation of smooth muscle (mainly vascular) which results from release of NO.

Front 44

Which drug inhibits the ACh carrier (carrier which puts ACh into vesicles)

Back 44

Vesamicol

Front 45

What is tubocurarine

Back 45

A drug that blocks postsynaptic ACh receptors. It is a non-depolarising blocking agent.

Front 46

What are the types of postsynaptic potentials? Include time for transmission for each

Back 46

Slow IPSP (I is for inhibitory) are aka hyperpolarising and last 2-5s. M2 receptors play main role buth other transmitters do too.

Slow EPSP last for 10 seconds and is produced by ACh acting on M1 receptors.

Late slow EPSP lasts for 1-2 minutes. Also M1 receptors.

Front 47

What is depolarization block?

Back 47

Occur when excitatory nAChRs are persistently activated because of a decrease in the electrical excitability of the postsynatpic cell

Front 48

Application of nicotine to a sympathathetic ganglion has what effect?

Back 48

Depolarizes the cell which at first causes an action potential but after a few minutes the transmission is blocked.

Front 49

What does Hemicholinium do?

Back 49

Blocks the choline carrier

Front 50

Neostigmine is a drug which?

Back 50

Blocks AChEsterase

Front 51

Which drugs are cholinergic agonists?

Back 51

Bethanechol *
Carbachol
Pilocarpine *
Methacholine
Nictoine
ACh

* Ones used clinically. They act on both mAChR and nAChR but on the previous one more potently.

Front 52

Which receptor is responsible for the parasympathetic reflex necessary to accommodate the eye for near vision?

Back 52

mAChR -> contraction of ciliary body-> relaxing tension on

Front 53

What is the main use of muscarinic agonists clinically?

Back 53

Treatment of glaucoma in the form of eye drops. Pilocarpine is the most effective to do this.

(Remember sympathetic innervation of constrictor pupillae leads to dilation which causes blockage of Schlemm canal)

Front 54

Although used rarely, Bethanechol is also used as a drug. Do you know what for?

Back 54

Assist bladder emptying or to stimulate GI motility. It acts on M3 receptors

Front 55

What are the pharmacological properties of atropine? Clinical uses? Side effects?

Back 55

Non-selective muscarinic antagonist. Well absorbed orally.

Adjunct for anesthesia, bradycardia, Anticholinesterase poisoning

Side Fx: urinary retention, dry mouth, blurred vision

Front 56

Which drug has similar actions and uses to atropine?

Back 56

Scopolamine. It is used for the same clinical uses as atropine + treatment for motion sickness

Front 57

Apart from atropine and scopolamine , what are some other muscarinic antagonists?

Back 57

1) Atropine methonitrate (lacks CNS effects of atropine) used for GI hypermotility

2) Tropicamide. Opthalmic use to produce mydriasis and cycloplegia

3) Pirenzepine - Selective for M1 - treatment of peptic ulcer

4) Darifenacin - Selective for M3 - treatmnt of urinary incontinence

Front 58

What effect does atropine have on the CNS? Poisoning?

Back 58

Mainly excitatory. Atropine poisoning causes excitement and irritability with a rise in body temperature and loss of sweating. This all results from blocking the mAChR in the brain.

Front 59

Which drugs would one use to treat atropine poisoning?

Back 59

Anticholinesterases such as physostigmine

Front 60

Which drugs affect the autonomic ganglia preferntially ?

Back 60

1) Nicotine
2) Lobeline
3) Dimethylphenypiperazinium (DMPP)

Only Nicotine is used clinically to help people stop smoking.

Front 61

What was the first antihypertensive treatment?

Back 61

Hexamethonium. It is no longer in use.

Front 62

What is the only ganglion-blocking drug currently in clinical use?

Back 62

Trimetaphan

Front 63

What is a ganglion-blocking drug? How do they work?

Back 63

A drug that inhibits post synaptic transmission in ganglia by binding the nicotinic receptors of both para and sympathetic ganglia.

Any one/combo:
- Interference with ACh release (botulinum toxin, hemicholinium)
- Prolonged depolarization (Nicotine and ACh(if cholinesterase is inhibited))
- Interference with postsynaptic action of ACh (blocking neuronal nAChRs)

Front 64

Which drugs undergo zero-order elimination?

Back 64

PEA

Phenytoin
Ethanol
Aspirin

Front 65

What is acetylcholine used for ?

Back 65

To achieve miosis during opthalmic surgery.

Front 66

What are the side effects of all cholinergic agonists (incl. acetylcholine) ?

Back 66

DUMBBELSS

Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation

Front 67

Neostigmine

Does it enter the CNS?
Indications
Adverse effects

Back 67

No it does not.

Myasthenia gravis, urinary retention, postoperative/neurogenic ileus, antidote for non-depolarising neuromuscular junction blockade.

Same as excessive chol. stim.

Front 68

What does Carbachol do?

Back 68

Rarely used but it is used for glaucoma and to stimulate miosis during surgery.

Front 69

What are the effects of pilocarpine? Which receptors does it work on? Adverse effects?

Back 69

Causes miosis and contraction of ciliary muscle + other regular parasympathetic activities. It is resistant to cleavage by AChE.

Primarily M receptors.

Adverse FX:
Unline the other direct agonists in this category it is able to enter the brain and cause CNS disturbances (hallucinations, convulsions)

Front 70

What is methacholine used for? Receptors? Adverse effects?

Back 70

Diagnosis of asthma and hyperactivity in the bronchus

M receptors

Like those of general cholinergic stimulation

Front 71

What are the common indirect cholinergic agonists (6) ? (anticholinesterases)

Back 71

PEEPIN

Isoflurophate
Echothiphate
Parathion
Edrophonium
Physostigmine
Neostigmine

Front 72

Which indirect cholinergic agonist can irreversibly inhibit AChE?

Back 72

Organophosphates. They bind covalently.

(isoflurophate, echothipate..)

Front 73

What are isoflurophate and echothiophate used for?

Back 73

Occasionally for glaucoma

Front 74

How is cholinesterase inhibitor poisoning treated?

Back 74

Atropine with pralidoxime ( chemical antagonist used to regenerate active cholinesterase )

Front 75

Physostigmine

Indications
Adverse effects

Back 75

Glaucoma ( second choice after pilocarpine) . It enters the CNS.

Overdoses of atropine, phenothiazines, tricyclic antidepressents

Adverse:
- Convulsions
- Muscle paralysis from overstim.
- Cataracts
+ all other symptoms of excessive ACh.

Front 76

Edrophonium

Clinical use
Adverse fx

Back 76

Used in the diagnosis of myasthenia gravis and its differentiation from cholinergic crisis. Short acting (5-15min)

Same as excessive chol. stim.

Front 77

Pyridostigmine

Clinical use
Adverse FX

Back 77

Long term treatment of myasthenia gravis

Same as excessive chol...

Front 78

What are 6 muscarinic blockers?

Back 78

Atropine
Scopolamine
Homatropine
Tropicamide
Pirenzepine

Front 79

Which drugs that are not specifically muscarinic antagonists possess antimuscarinic properties ?

Back 79

1) Benzotropine (treatment of Parkinsons)
2) Ipratropium (anti-asthmatics)
3) Thorazine (anti depressent)

Front 80

Atropine

Mechanism
Actions
Uses
Contraindications
Toxic effects
Antidote

Back 80

Reversible, nonselective blockade of muscarinic receptors

CNS- hallucinations/restlessness at high doeses.Does not cross BBB.

CV - Low dose - reduces HR . High dose- blocks muscarinic in heart and causes tachycardia

Suppresses sweating.

Uses:
- Bradycardia
- Eye drops ( mydriasis, cyclopleg.)

Contraindicated in people with with narrow-angle glaucoma

Toxic: Dry as a bone, (xerostomia), Hot as a hare (inhibiton of sweating), Red as a beet ( tachycardia , cutaneous vasodilation), Blind as a bat (blurring), Mad as a hatter (hallucinations)

Antidote = high [ ] of ACh or agonist

Front 81

Scopolamine

Mechanism
Use
Route

Back 81

Nonselective competitive blockade

Motion sickness
Transdermally given

Front 82

Homatropine and Tropicamide

Use

Back 82

Given to cause mydriasis and cycloplegia

Front 83

Name four nondepolarizing blockin g agents (subgroup of neuromuscular blocking agents)

Mechanism
Use
Route
Adverse effects
Antidote

Back 83

Tubocurarine
Pancuronium
Atracurium
Vecuronium

Competitvely block cholinergic transmission at the nicotinic receptors

Adjuvants for anesthesia - promote muscle relaxation

- IV

- Bronchoconstriction and hypotension (histamine release)

- Edrophonium or neostigmine

Front 84

Name the only depolarizing neuromuscular blocking agent in use in the USA?

Back 84

Succinylcholine

Front 85

Succinylcholine

Mechanism
Metabolism
Use
Adv. Effects

Back 85

Phase 1 - Succinylcholine binds to nAChR, opens Na channels -> depolarization -> transient fasiculations leading to prolonged depolarization ( AChE resistant)
Phase 2 - Membrane partially repolarizes but receptor is now desensitized to ACh = no more action potentials

- Plasma cholinesterase

- Adjuvant to general anesthesia and for rapid intubation

- Adv. effects: Bronchoconstrict. (histamine release), Hypotension/bradycardia, Arrythmias (due to potassium release), Apnea, malignant hyperthermia , Increased intraocular pressure, prolonged paralysis

Front 86

Do neuromuscular blocking agents block autonomic ganglia too?

Back 86

No. They use different nicotinic receptors. Tubocurarine may produce a small amount of ganglionic blockade.

Front 87

Name four ganglionic blockers
Mechanism
Effects

Back 87

Nicotine
Hexamethonium
Mecamylamine
Trimethaphan

Compete with ACh to bind with nicotinic receptors of both para and symp. ganglia. Nicotine stimulates the ganglia and then blocks them because of persistent depolarization. Drugs like hexameth. mecamyl. and trimetaphan block the ganglia without any prior stimulation.

Heart - Tachycardia ( parasymp is normally dominant)
Vascular - Vasodilation
Eye - Cyclopegia, mydriasis
GI - Reduced motility ; decreased secretions.
Urinary - retention
Sweat - reduced sweating

Front 88

When is neuromuscular block used?

Back 88

As an adjunct to anesthesia. It is not a therapeutic intervention.

Front 89

What is tetanic fade?

Back 89

a term used to describe the failure of muscle tension to be maintained during a brief period of nerve stimulation at a frequency high enough to produce a fused tetanus. It occurs mainly due to the block of presynaptic nAChRs. It does not occur with a depolarising block.

It i increased by non-depolarising blocking drugs compared to normal.

Front 90

Characteristics of non-depolarising and depolarising neuromuscular-blocking drugs

Back 90

-non-depolarising is reversible by anticholinesterase drugs , depolarising is not
- depolarising block produces initial fasciculations and often postoperative pain

Front 91

What is malignant hyperthermia? Which drugs are implicated? Treatment?

Back 91

Rare inherited condition, due to a mutation of the ryanodine receptor ( Ca release channel of SR). Results in intense muscle spasm and dramatic rise in body temperature when certain drugs are given.

Succinylcholine and halothane

Treatment by administration of dantrolene (prevents Ca release from SR)

Front 92

Which agents inhibit Ca entry into the presynpatic neuron?

Back 92

Mg2+

Aminoglycoside antibiotics (streptomycin and neomycin) -> sometimes cause muscle paralysis clinically

Front 93

What two toxins inhibit ACh release? Mechanisms? Treatments?

Back 93

Botulinum toxin
- Contains peptidases that cleave proteins involved in exocytosis.
- Treatment involves antitoxin but must be given before symptoms
- Used to treat blepharospasms as well as other spasms. Wrinkles 2.

B-bungarotoxin
- Contains a phospholipase rather than a peptidase

Front 94

What are the two types of cholinesterase? Locations? Specificity?

Back 94

Acetylcholinesterase and butyrylcholinesterase.

Soluble form of AChE is found in CSF and in cholinergic nerve terminals ( monitors free ACh? ). BuChE is found in plasma in soluble form. Bound form of AChE is found in cholinergic synapses (hydrolysis activity)

AChE is quite specific for ACh and methacholine

BuChE is widespread (not only in cholinergic synapses). Function is unclear. Hydrolyses a broader substrates ( butrylylcholine, procaine, succinylcholine, propanidid) [plasma form is important for this]

Front 95

Which is the only important short acting anticholinesterase? Use?

Back 95

Edrophonium. Used for diagnostic purposes ( improvement of muscle strength using anticholinesterase is characteristic of myasthenia gravis)

Front 96

List the medium-duration anticholinesterases

Back 96

Neostigmine
Pyridostigmine
Physostigmine

Front 97

List some irreversible anticholinesterases

Back 97

Dyflos
Parathion
Ecothiopate

Front 98

What are the effects of anticholinesterase drugs

Back 98

Affects autonomic cholinergic synapses and neuromuscular junctions. ( just think )

CNS effects - convulsions , depression

Front 99

Donepezil is an example of what kind of drug

Back 99

Anticholinesterase used to treat Alzheimer's disease

Front 100

What are ecothiopate eye drops?

Back 100

Anticholinesterase drops used to treat glaucoma

Front 101

Which drugs enhance cholinergic transmission?

Back 101

Tetraethylammonium
Aminopyridines..

They are not selective enough to be used clinically.

Front 102

Name the important alpha-selective direct-acting agonists (4)

Back 102

1) Phenylephrine (a1 receptor)
2) Methoxamine (a1 receptor)
3) Oxymetazoline (a1 receptor)
3) Clonidine (a2 receptor)
4) Methyldopa (a2 receptor)
5) a-methylnoradrenaline (a2)

Front 103

What are the major B selective direct-acting agonists ?

Back 103

Dobutamine (b1)
Isoproterenol (both b1 and b2)
Orciprenaline (b2)
Terbutaline (b2)
Salbutamol (b2)
Salmetrol (b2)

Front 104

What are the major alpha and beta direct-acting agonists?

Back 104

Epinephrine
Norepinephrine
Dopamine

Front 105

Which direct-acting agonists are considered catecholamines ?

Back 105

Epinephrine
NE
Dopamine
Isoproterenol
Dobutamine

Front 106

Name two indirect-acting adrenergic agonists

Back 106

Tyramine and amphetamine

Front 107

Two mixed (direct and indirect) agonists

Back 107

Ephedrine
Metaraminol

Front 108

Where are alpha-1 and alpha-2 receptors located?

Back 108

alpha 1 = postsynaptic membrane
alpha 2 = predominantly on presynaptic membrane (a2 can be found postsynaptically in CNS and blood vessels)

Front 109

What are the responses to alpha-1 and -2 stimulation?

Back 109

alpha-1 = release of intracellular calcium via IP3 (Gq protein**) -> sympathetic effects you know (vasoconstriciton etc.).

alpha-2 = cAMP production inhibition (Gi protein). Actions:
1) NE in synapses can bind to the presynpatic receptors and inhibit further release (negative feedback)
2) Suppressed insulin secretion
3) Increased vagal tone
4) Platelet aggregation

Front 110

Phenylephrine

Action
Uses
Adverse effects

Back 110

Primarily vasoconstriction.

Nasal decongestant (primary)
Hypotension treatment
To terminate episodes of paroxysmal atrial tachycardia

Rebound mucosal swelling and hypertensive headache

Front 111

Methoxamine

Use
Adverse effects

Back 111

Treatment of hypotension and paroxysmal atrial tachycardia

Similar to phenylephrine

Front 112

Clonidine

Use
Adverse effects

Back 112

- Treatment of hypertension
- Withdrawal from benzos and opiates
- Treatment of diarrhea in diabetic patients

1) Sedation
2) Dry mouth
3) Sexual dysfunction
4) Orthostatic hypotension

Front 113

Where are B-receptors found? What occurs from their activation?

Back 113

B1 = postsynaptic membrane
B2 = pre and postsynaptic

B1 ->Gs-> open Ca channels -> cardiac stimulation and increased lipolysis

B2 ->Gs -> " " -> bronchial smooth muscle + skeletal muscle vasculature dilation, glucagon release is increased, detrusor muscles are relaxed and uterus too.

Front 114

What do both B1 and B2 receptors produce?

Back 114

Decreased intestinal tone and motility (alpha receptors cause this too)

Front 115

Dobutamine

What is it?
Receptors
Effects
Use
Adverse effects

Back 115

Dopamine analogue

Primarily B1 but some action on B2

Increases HR and contractility (b1) and smooth muscle relaxation (b2)

Treatment of unstable CHF and shock

Arryhthmias, Headache, HTN, Palpitations, Angina, Nausea

Front 116

Isoproterenol

Receptors
Actions
Use
Adverse effects

Back 116

B1 and B2 receptors

Increases CV inotropic and chronotropic effect (B1), lowers peripheral vascular resistance (B2), Relaxes smooth muscles (B2)

HR stimulation in heart block and bradycardia

Arrhytmias
Palpitations
Tachycardia
Headache

Front 117

Albuterol, Metaproterenol, Terbutaline

Receptors
Actions
Uses
Adverse Effects

Back 117

B2 receptors but can stimulate B1 at higher doses

Stimulation of smooth muscle dilatation

- Treatment of bronchospasm
- Treatment of COPD
- Treatment of bronchitis
- Terbutaline + ritodrine can be used to relax uterus during premature labor.

Arrhythmias
Tachycardia
Headache
Nausea

Front 118

Epinephrine

Receptors
Action
Use
Adverse

Back 118

All 4 receptors. Low dose -> B receptors and at high doses -> A receptors.

- CV - Increased HR and contractility
- Resp. - Bronchodilation (B2)
- Metabolic - Increased glycogenolysis and release of glucagon

a) Bronchospasm secondary to asthma
b) Anaphylaxis and cardiac arrest
c) Prolongation of drug effects via vasoconstriction
d) to achieve hemostasis

Arrhythmia
HTN
Palpitation
Tremor
Dizziness
MI
PE

Front 119

What is epinephrine reversal ?

Back 119

When EPI is given alone it causes an increase in BP through alpha receptors. When it is given with an alpha-blocker it will cause a decrease in BP because of its B2 activity.

Front 120

Which receptors does norepinephrine bind to?

Back 120

A1,A2,B1 receptors. NE has a stronger affinity for alpha-receptors than Beta r.

Front 121

Norepinephrine

Action
Use
Adverse effects

Back 121

Vasoconstriction, reflex bradycardia

Shock (last-line agent)

- Tissue hypoxia ( due to vasoconstriction being strong)
- Decreased kidney perfusion
- Arrhythmias

Front 122

Dopamine

Where is it found
Receptors
Use
Adverse effects

Back 122

Synthesized in CNS, sympathetic ganglia and adrenal medulla

A1,B1,B2, D1,D2
(D receptors at low dose, B receptors at moderate dose, A1 receptors at higher doses)

Treatment of shock (raises BP via b1) , acute renal failure (increased BF), acute CHF.

- Arrhytmia, Tachycardia, HTN

Front 123

Tyramine

Action
Use
Adverse

Back 123

by-product of tyrosine metabolism

Tyramine is taken up by sympathtic neurons -> release of catecholamines

No therapeutic use

Hypertensive emergency when given to patients taking MAO inhibitors

Front 124

Amphetamine

Actions
Use
Adverse effects

Back 124

Releases store of NE and dopamine

Treats ADHD and narcolepsy and appetite suppression

Dependence
Psychosis
and so on..

Front 125

Ephedrine

Action
Use
Adverse

Back 125

Stimulates release of NE from nerve terminals. Also acts as a direct adrenergic agonist.

Urinary incontinence, bronchospasm, hypotension

Arrhythmias, Palp., Insomnia , HTN

Front 126

Metaraminol

Actions
Use
Adverse

Back 126

Indirectly releases NE. Stimulates alpha receptors too

Treatment of hypotension and PAT episodes

Similar to those of norepinephrine

Front 127

List 6 alpha blockers

Back 127

1) Prazosin - a1 adrenergic
2) Doxazosin- a1
3) Terazosin- a1
4) Phenoxybenzamine - nonselective,*irreversible* only one!!
5) Yohimbine- a2
6) Phentolamine - nonselective

Front 128

Prazosin, Terazosin, Doxazosin

Action
Effect
Use
Adverse FX

Back 128

Competitively blocks a1 receptors

In vascular sm it inhibits constricton of arterioles and venules -> decreased TPR and lower BP. In bladder, there is relaxation and decreased resistance to urine flow

Treatment of HTN and prevention of urinary retention in patients with benign prostatic hypertrophy

GI hypermotility , Orthostatic HTN (after initial dose especially), sexual dysfunction, dry mouth, dizziness

Front 129

Phenoxybenzamine

Action
Effects
Duration
Use
Adverse FX
Contraindications

Back 129

Noncompetitively blocks a1 postsynaptic receptors and a2 presynaptic receptors.

Blocks peripheral vasoconstriction and induces reflex tachycardia

Very long. Covalently binds to receptor

a) Treatment of patients with pheochromocytoma-indcued HTN
b) Treatment of patient with benign prostatic hypertrophy. It reduces the size of the prostate
c) Treament of spinal cord injury induced hyperreflexia leading to high bp
d) Treatment of Raynaud's disease

Orthostatic hypotension, Reflex tachycardia, Inhibition of ejaculation

Patients with CAD

Front 130

What is the use of Yohimbine?

Back 130

Treat impotency via penile injection

Front 131

Phentolamine

Mechanism
Use
Adverse effects

Back 131

Reversibly blocks a1 and a2

Short term control of pheochromocytoma HTN

Orthostatic hypotension, GI stimulation which may lead to peptic ulcers, tachycardia, MI or arrhythmias

Front 132

What are B blockers? How can they be subclassified?

Back 132

Competitive antagonists

1. Selectivity of receptor blockade
2. Possession of intrinsic sympathomimetic activity
3. Capacity to block a-adrenergic receptors

Front 133

Name four selective B1 blockers. Are they really fully selective of B1?

Back 133

Atenolol
Esmolol
Acebutolol
Metoprolol

* B-blockers starting with A or M are usually cardioselective

No. At high doses these drugs will block B2 receptors

Front 134

What is the advantage of B1 selectivity

Back 134

They are sometimes called cardioselective because they lack unwanted bronchoconstrictor and hypoglycemic effects of nonselective blockers

Front 135

For the four B1 blockers mentioned in another slide, what is the use of each one?

Back 135

Atenolol - for HTN, MI
Esmolol - For immediate B blockade
Acebutolol - HTN
Metoprolol - HTN, angina pain, MI

Front 136

What is the prototpe non-selective B-blocker?

Back 136

Propranolol

Front 137

What are the actions of nonselective B-blockers?

Back 137

Decreased CO and BP

Reduction of sinus rate and conduction through atria

- Peripheral vasoconstriction
- Bronchoconstriction
- Decreased glycogenolysis and glucagon secretion
- Increased VLDL and decreased HDL

Front 138

Propranolol

Site of metabolism
Absorption

Back 138

Liver

Compeletly absorbed after oral but only 25% reaches blood (first-pass metabolism)

Front 139

Indications for nonselective B-blockers

Back 139

HTN
Angina, tachycardia
Arrhythmia
Thyroid storm
Migraines

Front 140

Timolol and Nadolol are what kinds of drugs? Use?

Back 140

nonselective b-adrenergic antagonists

Treatment of glaucoma (decrease production of aqueous humor production)

Front 141

Adverse effects of nonselective B-blockers

Back 141

Bradycardia
Bronchoconstriction
Hypoglycemia
Fatigue
Depression
Sexual dysfunction

Front 142

Acebutolol and pindolol are examples of what kind of drugs? Use? Advantages?

Back 142

B blockers with intrinsic sympathmimtic activity. They are considered partial agonists as they very mildly stimulate both B1 and B2 receptors.

Treatment of HTN in patients prone to bradycardia

They do not induce bradycardia like full antagonists do and produce bronchoconstriction only at very high doses.

Front 143

Labetalol

Classification
Mechanism
Clinical use
Adverse effects

Back 143

Nonselective B-blocer with a1 adrenergic selective blockade

By blocking both those receptors, peripheral vasodilation rather than vasoconstriciton occurs (unlike other b-blockers)

Treatment of HTN and atrial fib.

Orthostatic hypotension and dizziness

Front 144

Any drugs similar to Labetalol? Use? Action? Contraindications?

Back 144

Carvedilol (B blocker with a1 blocking properties)

Treatment of HTN
Treatment of chronic CHF (reduce sympathetic activity)

- Reduction of sympathetic activity
- Improvement of diastolic dysfunction bu prolonging filling time

- Contraindicated in ACUTE CHF.

Front 145

Name one B2 selective blocker

Back 145

Butoxamine

It is not used clinically

Front 146

Name two indirect adrenergic antagonists. How do they work?

Back 146

Guanethidine and Reserpine.

They block the release of NE from nerve endings - in effect, antagonizing the effects of the sympathetic system

Front 147

Guanethidine

Mechanism
Use
Adverse effects

Back 147

Enters peripheral adrenergic nerves by a reuptake mechanism for NE and binds to storage vesicles

Treatment of HTN

Orthostatic hypotension and sexual dysfunction

Front 148

Reserpine

Mechanism
Use
Adverse effects

Back 148

Blocks NE transport from cytoplasm into intracellular storage vesicles.

Treating HTN (rarely used)

CNS depression and bradycardia

Front 149

Where is most of the serotonin found in the body?

Back 149

1) In the wall of the intestine in enterochromaffin cells (>90%)

2) In blood ( in platelets)

3) In CNS (transmitter)

Front 150

What is the precursor of dopamine?

Back 150

Tryptophan

Front 151

Tryptophan is converted into 5-HT in which areas?

Back 151

In neurons and chromaffin cells but NOT platelets. Platelets contain a 5-HT uptake mechanism which allows platelets to get loaded as they pass through the intestinal circulation

Front 152

How is 5-HT degraded?

Back 152

MAO

Front 153

Mechanism of serotonin release in GI tract? Physiological inhibition?

Back 153

5-HT is released from enterochromaffin cells into the lamina propria, where it stimulates receptors on enteric neurons

Gut contains serotonin uptake transporterwhich removes 5-HT.

Front 154

5-HT1 receptors

Location, Action

Back 154

Location : Mainly in the brain

They function mainly as inhibitory presynaptic receptors and are linked to inhibition of adenylate cyclase

Front 155

What is special about the 5-HT1D subtype? Drug affecting this receptor?

Back 155

It is expressed in cerebral blood vessels and it is believed to be important in migraine.

Sumatriptan (agonist used to treat acute attacks)

Front 156

5-HT1 receptors affect cerebral vessels in an unusual way. Why?

Back 156

They cause vasoconstriction where in most vessels.. 5-HT2 receptors are responsible for this.

Front 157

5-HT2 receptors

1) Where are they important
2) Effects
3) When is it important

Back 157

1) In the periphery
2) Effects on smooth muscle and platelets (5-HT2A)
3) Minor role physiologically but prominent in pathology (asthma etc.)

Front 158

What is the only 5-HT receptor that is not a GPCR?

Back 158

5-HT3. This is a ligand-gated ion channel

Front 159

5-HT3

Where? Action

Back 159

Mainly in peripheral , particularly on nociceptive sensory neurons.

Strongly excitatory

Front 160

5-HT4

Action

Back 160

Main role in GI tract producing neuronal excitation and mediating the 5-HT effect of stimulating peristalsis

Front 161

What are the important actions of 5-HT?

Back 161

- Increased GI motility (direct action on smooth muscle and indirect via enteric neurons)

- Contraction of other sm (bronchi.etc)

- Mix of vasoconstriction and dilatation

-Platelet aggregation
- Stimulation of peripheral nociceptive nerve endings
- Excitation/inhibition of CNS neurons

Front 162

What are the role of 5-HT in the periphery?

Back 162

Peristalsis, vomiting, inflammatory mediator, nociception, platelet aggregation

Front 163

What does disturbed 5-HT function give rise to?

Back 163

Migraine
Carcinoid syndrome
Mood disorders
Anxiety

Front 164

What are some 5-HT2 antagonists? (3)

Uses

Back 164

1) Ergotamine
2) Methysergide
3) Cyproheptadine

1) Migraine treatment
2) Migraine prophylaxis +carcinoid syndrome
3) Control symptoms of carcinoid
tumors

Front 165

5-HT3 receptor antagonist (3)
1) Use

Back 165

Ondansetron
Granisetron
Tropisetron

1) Used as antiemetic drugs

Front 166

5-HT4 receptor agonists include (2)

Action

Back 166

Metoclopramide
Tegaserod

Stimulate coordinated peristaltic activity. Used from treating GI disorders.

Front 167

What drugs are used for acute migraine attacks?

Back 167

- Simple analgesics (ex. aspirin)
- Ergotamine (5-HT1D partial agonist)
- Sumatriptan, zolmitriptan (5-HT1D agonist)

Front 168

Which drugs are used for the prophylaxis of acute migraines?

Back 168

- B-adrenceptor antagonists (propanolol, metoprolol)
- Pizotifen (5-HT2 receptor antagonist)
- Cyproheptadine (5-HT2 antag.)
- Methysergide (5-HT2 antag)
- Tricyclic antidepressants
- Clonidine (a2 agonist)
- Calcium antagonists

Front 169

What is carcinoid syndrome?

Back 169

Rare disorder associated with malignant tumors of enterochromaffin cells. They release 5-HT and other mediators.

Front 170

P1 and P2 receptors are responsible for what?

Back 170

P1 respond to adenosine
-subtypes: A-1,2,3
P2 respond to ATP and/or ADP
- subtypes: P2x (ATP) and P2y (ATP,ADP)

Front 171

ATP

Function
ATP receptor antagonist

Back 171

Primary neurotransmitter and/or a cotransmitter in noradrenergic nerve terminals.

Suramin

Front 172

What occurs once ATP is released from the cell?

Back 172

It is rapidly converted into ADP and adenosine

Front 173

What is adenosine uptake blocked by?

Back 173

Dipyridamole

Front 174

Effects of adenosine

Back 174

- Vasodilatation (A2)
- Inhibition of platelet aggreg (A2)
- Blocks cardiac AV conduction (A1)
- Bronchoconstriction(A1)
- Release of mediators from mast cells (A3)
- Inhibitor of transmitter release at many peripheral and central synapses (A1)

Front 175

What may adenosine be administered for?

Back 175

To terminate supraventricular tachycardias. It is safer than B-blockers and verapamil

Front 176

Which drugs inhibit A1 and A2 adenosine receptors?

Back 176

Xanthines such as theophylline

Front 177

NSAIDS

1) Therapeutic effects
2) Side effects

Back 177

1) Anti-inflammatory , Analgesic , Antipyretic

2) Gastric irritation (ulcers), RBF effected in compromised kidney, prolong bleeding through inhibition of platelet function, skin rashes

Front 178

Most traditional NSAIDs inhibit which enzymes? Effect?

Back 178

COX-1 and COX-2

Inhibition of COX-2 is believed to cause the anti-inflammatory action

Inhibition of COX-1 is believed to be responsible for the side effects experienced

Front 179

What is the mechanism behind NSAIDs ability to be anti-inflammatory, analgesic and antipyretic?

Back 179

Anti-inflammatory - decrease in PGE2 and PGI2 reduces vasodilation and edema

Analgesic - Decreased PG generation -> less sensitisation of nociceptive nerve endings to inflammatory mediators like bradykinin and 5-HT

Antipyretic - IL-1 release PG in the CNS where they elevate the set point for temp. NSAIDs prevent this.

Front 180

List some important NSAIDs

Back 180

Aspirin
Ibuprofen
Naproxen
Indometacin
Piroxicam

Front 181

What type of inhibitors are most NSAIDs? Which reaction of the COX enzyme do most inhibit? Mechanism?

Back 181

Competitive reversible inhibitors (exception: Aspirin = irreversible acetylation of serine)

The dioxygenation reaction

NSAIDs enter the hydrophobic channel of COX enzymes and prevent substrate FA from entering

Front 182

NSAIDs' antiplatelet activity is due to what?

Back 182

Decreased production of thromboxane. This effect lasts 7 days ( life span of platelet)

Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation

Front 183

What are six groups of NSAIDs and give examples of each

Back 183

Salicylates:
- Aspirin
- Diflunisal
- Salsalate
Pyrazolones:
- Phenylbutazone (very toxic)
Indoleacetic acids:
- Indomethacin
- Sulindac
- Etodolac
- Ketorolac
Propionic Acids:
- Naprosen
- Ketoprofen
- Ibuprofen
Oxicams:
- Piroxicam
Fenamates:
- Mefenamic acid
- Meclofenamic acid

Front 184

What serious renal effect does chronic NSAID consuption/abuse cause?

Back 184

Analgesic nephropathy characterised by chronic nephritis and renal papillary necrosis

Front 185

Give examples of NSAIDs that would be given clinically for short-term pain releif and long-term

Back 185

Short term: aspirin, ibuprofen, paracetamol

Chronic pain: difunisal, naproxen, piroxicam

Front 186

Where does absorption of aspirin occur?

Back 186

It is is protonated (making it neutral) in the stomach, thus facilitating passage across the mucosa. However, most absorption occurs in the ileum.

Front 187

What unwanted effects are specific in aspirin and other salicylates?

Back 187

Salicylism characterized by tinnitus, vertigo, decreased hearing , and vomiting and nausea

Reye's syndrome, disorder of children characterized by hepatic encephalopathy followed by an acute viral illness.

Front 188

What are some important interactions of aspirin ? Contraindicated?

Back 188

Increases the effect of warfarin
Interferes with the effect of uricosuric agents

Should not be used in gout (reduces urate excretion)

Front 189

What usually occurs at toxic doses of aspirin (like suicide attempts)?

Back 189

Uncompensated respiratory and metabolic acidosis .

Compare with large doses which cause salicylism and with therapeutic doses usually gastric distress

Front 190

What are the unwanted effects of paracetamol (acetaminophen)

Back 190

Therapeutic dose - few effects and uncommon

Toxic doses - Nausea + vomiting at first and then fatal hepatotoxicity caused by build up of metabolite N-acetyl-p-benzoquinone imine .


Agents that increase glutathione ( used to make a conjugate for drugs) can prevent liver damage if given early

Front 191

Which drugs are COX-2 selective inhibitors?

Back 191

The coxibs. Very rarely used because of CV risks.

Front 192

What does the word antihistamine refer to?

Back 192

H1 receptor antagonist

Front 193

Action of antihistamines

Back 193

Decrease histamine-mediated contraction of sm of bronchi, intestine and uterus.

Front 194

H1 receptor antagonists show affinity for what type of other receptor (Not H1)

Back 194

Muscarinic, although lower than for histamine receptor. They act as muscarinic antagonists.

Front 195

What sort of action does cyproheptadine have?

Back 195

5-HT antagonist as well as an H1 receptor antagonist.

Front 196

What are the clinical uses of H1 receptor antagonists?

Back 196

Allergic reactions
- non-sedating drugs (fexofenadine, cetirizine) for rhinitin (hay fever) and urticaria
- topical preps for insect bites
- injectable formulas for anaphyl.

Antiemetics
- prevention of motion sickness

Sedation
- Some H1 antagonist (promethazine ( or SYZZURP) are fairly strong sedatives

Front 197

What are the clinical uses of immunosuppressants

Back 197

1) Suppress rejection of transplants
2) Suppress graft vs host in bone marrow transplants
3) Treat conditions with an autoimmune component

Front 198

Name some autoimmune diseases which can be treated using immunosuppression drugs?

Back 198

- Idiopathic thrombocytopenic purpura
- Hemolytic anemia (some forms)
- Glomerulonephritis (some forms)
- Myasthenia gravis
- SLE
- Rheumatoid arthritis
- Psoriasis
- Ulcerative colitis

Front 199

List the different classes of immunosuppressive drugs. Example of each?

Back 199

1) Drugs that inhibit IL-2 production/action (ciclosporin, tacrolimus)

2) Drugs that inhibit cytokine gene expression (corticosteroids)

3) Drugs that inhibit pure and pyrimidine synthesis (azathioprine , mycophenolate mofetil)

4) Drugs that block the T-cell surface molecules involved in signalling

Front 200

Ciclosporin

What is it
Actions
Mechanism

Back 200

It is a potent immunosuppressive with no effect on the acute inflammatory reaction. It does not involve cytotoxicity.

a) Decreased clonal proliferation of T cells by inhibiting IL-2 synthesis and possibly also decreasingexpression of IL-2 receptors
b) Reduced induction and clonal proliferation of cytotoxic T cells (CD8)
c) Reduced functon of effector T cells
d) reduction of T cell-dependent B cell responses

Ciclosporin binds to cyclophili ( an immunophilin) in the cytosol of Th cells. This complex then binds and inhibits calcineurin(phosphatase) that activates transcription factors initation IL-2 transcription.

Front 201

What is the most common and most serious adverse effect of ciclosporin? Other adverse effects?

Does ciclosporin depress the bone marrow?

Back 201

Nephrotoxicity

Hepatotoxicity and HTN, anorexia, lethargy, hirsutism, parasethsia , gum hypertrophy

No it does not.

Front 202

Tacrolimus -Compare to ciclosporin

Pimecrolimus and sirolimus - What are they and use

Back 202

More potent than ciclosporin. It does not bind to cyclophilin like ciclosporin but instead to a different immunophilin named FKBP . This complex inhibits clacineurin. More severe side effects with the incidence of nephrotoxicity and neurotroxicity being higher. GI and metabolic disturbances (hyperglycemia) also occur as side effects.

Pimecrolimus (used for atopic eczema) and sirolimus ( used to prevent organ rejection) are immunosuppressant with similar properties to tacrolimus

Front 203

Glucorticoids

Purpose in immunosuppression
Action

Back 203

Immunosuppression is mediated by both effects of glucorticoids (effects on immune response and anti-inflammatory response). They are immunosuppressant chiefly.

Decrease transcription of IL-2 but also of many other ones (incl. TNF-a, IFN-y, IL-1 etc.) in both the induction and effector phases of the immune response. This does this throguh inhibiting the action of transcription factors (such as activator protein-1 and NF kB)

Front 204

Azathioprine

Action
Use
Mechanism
Which immune reactions are depressed by this drug?
Unwanted effects?

Back 204

Intereferes with purine synthesis and is cytotoxic

Used particuarly for control of autoimmune disease and to prevent tissue rejection.

The drug is metabolised to give mercaptopurine which is a purine analogue that inhibits DNA syntheis.

Both cell and antibody-mediated because it inhibits clonal proliferation during the induction phase.

Depression of bone marrow (main unwanted effect), anausea, vomiting etc.

Front 205

Mycophenolate Mofetil

Mechanism
Use

Back 205

It is converted into mycophenolic acid which restrains T and B lymphocyte proliferation and reduces the production of CD8 T cells by inhibiting inosine monophosphate dehydrogenase (crucial for de novo purine biosynthesis in both T and B cells). This is the only way these cells can make them so the drug is fairly selective ( other cells can use other pathways)

To curtail transplant rejection

Front 206

What are the principal eicosanoids

Back 206

PGs , thromboxanes, leukotrienes

Front 207

Besides arachidonic acid, PLA2 also generates something else. Do you know what?

Back 207

lysoglyceryl-phosphorylcholine . This is the precursor of PAF.

Front 208

Apart from PLA2 , what other enzyme can release arachidonate ?

Back 208

Two step process involving PLC and DAG lipase. It releases glycerol and arachidonate

Front 209

What is the main eicosanoid produced by platelets? vascular endothelium?

Back 209

TXA2 and PGI2 , respectively.

Front 210

What receptors do PGD2, PGF2a, PGI2, PGE2 and TXA2 bind to?

Back 210

DP,FP,IP,EP,TP respectively.

Front 211

PGD2

Actions

Back 211

Vasodilation
Inhibition of platelet aggregation
Bronchoconstrictor
Relaxes GI and uterine muscle

Front 212

PGF2a

Actions

Back 212

Myometrial contraction

Front 213

PGI2

Actions

Back 213

Vasodilation
Inhibition of platelet aggregation
Renin release and natriuresis

Front 214

TXA2

Actions

Back 214

Vasoconstriction
Platelet aggregation
Bronchoconstriction

Front 215

PGE2

Actions

Back 215

Contraction of bronchial and GI sm (EP1)

Pyrogenic (inducing fever) - final mediator of raising the temperature

Bronchodilation, vasodilation, GI relaxation (EP2)

Contraction of intestinal sm, inhibition of gastric acid secretion, increased gastric mucus secretion, inhibition of lipolysis and autonomic neurotransmitter release and stimulates the contraction of the pregnant uterus (EP3)

Front 216

Which prostaglandins are the most important in acute inflammation ? Chronic?

Back 216

PGE2 (predominates) and PGI2 (local tissue and vessels) and PGD2 from mast cells.

PGE2 and TXA2 from monocytes/macrophages

Front 217

How do prostanoids (PG and TXA2) produce vasodilation, increased permeability and pain

Back 217

Really they don't do it directly. They synergize with other vasodilators like histamine and bradykinin. (potentiate). They potentiate the effect of bradykinin by sensitizing afferent C fibers to the effects of noxious stimuli.

Front 218

What are some clinical uses of prostanoids?

Back 218

OB/GYN
- Termination of pregnancy (gemeprost, misoprostol)
- Induction of labour (dinoprostone or misoprostol)
- Postpartum hemorrhage (carboprost)

GI
- Prevent ulcers associated with NSAID use (misoprostol)

CV
- maintain patency of ductus arteriosus until surgical correction (alprostadil - PGE1)
- Inhibit platelet aggregation (epoprostenol-PGI2)
- Primary pulmonary HTN (epoprostenol)

Ophthalmic
- Latanoprost for glaucoma

Front 219

What are leukotrienes made by?

Back 219

White cells - leuko.

Front 220

Leukotrienes

Receptors
Actions of types
Cysteinyl-leukotrienes are of particular important in what type of inflammation?

Back 220

BLT (LTB4) and CysLT (rest)

LTB4 - potent chemotactic agent for neutrophils and macrophages, proliferation of macro and lympho and cytokine release

Cysteinyl-leukotrienes act on the respiratory system (bronchoconstriction, mucus secretion (+) and the CV system (vasodilation, constriction of coronary vessels)
LTD4 increases nasal blood flow and local vascular permeability

Asthma (LTB4 is important in all types)

Front 221

Source of PAF? Actions?

Back 221

Platelets stimulated with thrombin and most inflammatory cells

Vasodilation, Increased vascular permeability, chemotaxis and activation of leukocytes, activation of platelets and smooth muscle contraction

Front 222

Which CysLT-receptor antagonists are in use for the treatment of asthma?

Back 222

Zafirlukast and montelukast

Front 223

Which NSAID stimulates the synthesis of lipoxins?

Back 223

Aspirin

Front 224

What is PAF implicated in? (diseases)

Back 224

Bronchial hyperresponsiveness and delayed phase of asthma

Front 225

What are some lipooxygenase inhibitors ?

Back 225

Azelastine
Diethylcarbamazine
Nordihydroguaiaretic acid
zileuton

Front 226

What kind of receptors do most cytokines act on? Exception?

Back 226

Kinase-linked receptors (such as Jak/Stat)

Chemokines act on G-protein coupled receptors.

Front 227

Anti-inflammatory cytokines

Back 227

TGF-B, IL-4, IL-10, IL-13

Front 228

Drugs affecting gout act in which ways?

Back 228

Inhibit uric acid synthesis (allopurinol)

Increasing uric acid excretion (uricosuric agents - probenecid, sulfinpyrazone)

Inhibiting leukocyte migration to the joint (colchicine)

General anti-inflammatory and analgesic effect (NSAID)

Front 229

Allopurinol

Mechanism
Adverse effects
When not to treat
Interactions

Back 229

Competitive inhibition of xanthine oxidase reducing the synthesis of uric acid. Its action is due to alloxanthine (non-competitive metabolite inhibitor of allopurinol from xanthine oxidase.

GI disturbances and allergic reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis can occur as well

During an acute attack of gout

Increases the effect of mercaptopurine and azathioprine and cyclophosphamide. ( These are all anti-cancer drugs). The effect of warfarin is also increased because its metabolism is inhibited.

Front 230

Treatment of gout with uricosuric drugs and allopurinol is initiated with what accompanying drug?

Back 230

an NSAID.

Front 231

When are uricosuric agents used?

Back 231

Prophylaxis for patients with gout who have severe adverse reactions to allopurinol

Front 232

Colchicine

Mechanism
Use
Adverse

Back 232

Prevents migration of neutrophils into the joint by binding to tubulin and reducing cell motility by depolymerisation of microtubules.

To prevent and relieve acute attacks

GI problems : nausea , abdominal pain, diarrhea

Front 233

Drugs available for treating acute attack of gout?

Back 233

Indomethacin , Phenylbutazone, Colchicine

Front 234

Aspirin is an NSAID - can it be used in treatment of gout?

Back 234

NO! being a salicylate makes it inhibit uric acid secretion into the renal tubules . Contraindicated !!

Front 235

Which drugs are used to treat chronic gout?

Back 235

Allopurinol and Uricosuric agents

Front 236

Which drugs are most frequently used in the treatment of rheumatoid arthritis ?

Back 236

DMARDs and NSAIDs

Front 237

Besides DMARDs and NSAIDs what other drugs are used?

Back 237

Some immunosuppressants like azathioprine and ciclosporin and glucocorticoids

Front 238

What drugs fall under DMARDs?

Back 238

Methotrexate , Sulfasalazine, gold compounds, penicillamine, chloroquine

Front 239

Methotrexate

Mechanism

Back 239

Folic acid antagonist with cytotoxic and immunosuppressant activity

Front 240

What are the three isoforms of NOS? Characteristics

Back 240

iNOS (NOS-2) , eNOS (NOS-3), nNOS (NOS-1)

* eNOS isn't restricted to the endothelium (found also in cardiocytes, bone cells etc..)

* iNOS is also present in endothelial cells

nNOS and iNOS are soluble cytosolic enzymes

Front 241

What are the substrates for NOS?

Back 241

L-arginine and O2

Front 242

How is NO inactivated?

Back 242

By combination with heme of hemoglobin or by oxidation to nitrite and nitrate -> excreted.

Front 243

Which secondary messanger does NO use?

Back 243

cGMP

Front 244

The effects of cGMP are terminated by which enzymes?

Back 244

Phosphodiesterases

Front 245

Which drugs are inhibitors of phosphodiesterase type V ? What are they used for?

Back 245

Sildenafil and tadalafil. Treating erectile dysfunction because they potentiate NO action.

Front 246

Effects of NO

Back 246

- Autocrine and Paracrine action activating cGMP (by binding to heme of guanylate cyclase) which leads to inhibition of Ca -induced smooth muscle contraction (Vasodilation). NO also hyperpolarizes vascular smooth muscle

NANC neurotransmitter in many tissues. Important in upper airways, GI and control of penile erection. It is implicated in the neuronal development of synaptic plasticity in the CNS as well. (Synaptic effect in PNS and CNS)

Host defense (cytotoxic peroxynitrite when bound with superoxide anion)

Cytoprotection

Front 247

What do high concentrations of NO cause? What is the main action of inhaled NO? Use?

Back 247

Pulmonary edema and methemoglobinemia

Pulmonary vasodilation

Reduce pulmonary HTN and to improve O2 delivery in patients with ARDS

Front 248

Which drug inhibit the production of NO?

Back 248

Glucorticoids inhibit biosynthesis of iNOS

Synthetic arginine analogues

Endogenous NOS inhibitors (ADMA and PIN)

Front 249

What is a NO donor?

Back 249

glyceryl trinitrate

Front 250

What does NO and sepsis have to do with anything? What

Back 250

NO benefits host defence by killing organism but excessive NO causes harmful hypotension.

Front 251

Some other diseases NO may be implicated in?

Back 251

Underproduction of neuronal NO is seen in babies with hypertrophic pyloric stenosis.

NO production by the endothelium is reduced in patients with hypercholesterolemia and some other risks factors for atherosclerosis

Overproduction may be important in neurodegenerative disease (and sepsis :) )

Front 252

What are some nitric oxide donors?

Back 252

Nitroprusside and organic nitrovasodilators

Front 253

Failure to increase endogenous NO biosynthesis normally during pregnancy is thought to cause?

Back 253

Eclampsia, a hypertensive disorder that accounts for many maternal deaths

Front 254

Excessive NDMA receptor activation causes?

Back 254

Increases NO synthesis and contributes to several forms of brain damage

Front 255

Endothelial dysfunction in diabetic patients can cause..

Back 255

erectile dysfunction due to blunted relaxation to ACh despite preserved responses to nitroprusside

Front 256

Which prostaglandins *only ones* that decay rapidly without prostaglandin-specific enzymes?

Back 256

PGI2 and TXA2

Front 257

Formula for calculating bioavailability (F)?

Back 257

F=AUC(route)/AUC(IV)

Front 258

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 258

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

Front 259

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

Back 259

t1/2=0.693*Vd/Cl

Front 260

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

Back 260

Loading dose=(Vd*Cp)/F

Front 261

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 261

Maintenance dosage=(Cl*Cp)/F

Front 262

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

Back 262

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 263

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 263

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 264

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 264

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

Front 265

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

Back 265

metyrosine

Front 266

Monoamine oxidases (MAOs) are present where?

Back 266

On the mitochondria in nerve endings

Front 267

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

Back 267

They don't contain the endocytoic mechanism for taking up botulin toxin. Therefore they are not inhibited.

Front 268

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

Back 268

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 anatgonist

Front 269

Drug that blocks the uptake of ACh.

Back 269

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 270

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

Back 270

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 271

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

Back 271

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

Front 272

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

Back 272

1. Gq (smooth muscle, some glands), Gi (cardiac muscle).
2. Increases IP3 and DAG (Gq), decreases cAMP & opens K+ channels (Gi)

Front 273

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

Back 273

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

Front 274

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

Back 274

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

Front 275

G protein associated with, effect and second messenger of beta1, beta2, beta3 receptors

Back 275

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

Front 276

Effect of sympathetic discharge (and receptor type) on eye

Back 276

dilates pupil (α)

Front 277

Effect of sympathetic discharge (and receptor type) on airways

Back 277

dilates bronchioles (β2)

Front 278

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

Back 278

slows motility (α, β2)

Front 279

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

Back 279

contracts sphincters, mediates ejaculation (α)

Front 280

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

Back 280

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

Front 281

Effect of sympathetic discharge (and receptor type) on heart

Back 281

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

Front 282

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

Back 282

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

Front 283

Effect of sympathetic discharge (and receptor type) on metabolism (4)

Back 283

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 284

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

Back 284

1. increases strength (alpha)
2. causes tremor (beta2)

Front 285

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

Back 285

1. constricts pupil (M)
2. focuses for near vision (M)

Front 286

Effect of parasympathetic discharge (and receptor type) on airways

Back 286

constricts bronchioles (M)

Front 287

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

Back 287

increases motility, secretion (M)

Front 288

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

Back 288

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

Front 289

Effect of parasympathetic discharge (and receptor type) on vessels

Back 289

little effect

Front 290

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

Back 290

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

Front 291

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

Back 291

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 292

Effect of parasympathetic discharge (and receptor type) on metabolism

Back 292

little effect

Front 293

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

Back 293

little effect

Front 294

Clinical uses of cholinomimetics (6)

Back 294

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 295

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 are best remembered with the mnemonic

Back 295

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 296

Muscarinic receptor blockers are what kind of blockers?

Back 296

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

Front 297

Nicotinic receptor blockers are what kind of blockers?

Back 297

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 298

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

Back 298

Therapeutic doses:

1. sedation
2. some reduction of motion sickness
3. reduction of Parkinsonian tremor.

Toxic doses:

4. hallucinations
5. convulsions

Front 299

Actions and toxicities of muscarinic blockers on the eyes

Back 299

Marked mydriasis and cycloplegia.

Front 300

What is cycloplegia?

Back 300

loss of accomodation (due to paralysis of the ciliary muscle)

Front 301

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

Back 301

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

Front 302

Actions and toxicities of muscarinic blockers on the GI tract

Back 302

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

Front 303

Actions and toxicities of muscarinic blockers on the GU tract

Back 303

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

Front 304

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

Back 304

at therapeutic doses;

1. no effect on vessels
2. heart rate and AV conduction velocity usually increase due to vagal blockade.

High doses:

3. flushing of the skin

Front 305

Toxicities of ganglion blockers (5)

Back 305

1. cycloplegia
2. orthostatic hypotension
3. constipation
4. urinary retention
5. sexual dysfunction

Front 306

Modes of action of neuromuscular nicotinic blockers (2)

Back 306

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

Front 307

Mode of action and indications for nondepolarizing blockers

Back 307

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

Front 308

Toxicities of nondepolarizing blockers

Back 308

1. hypotension (from histamine release and ganglion blockade)
2. excessive neuromuscular block requiring prolonged respiratory support

Front 309

Six representative antimuscarinic drugs

Back 309

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

Front 310

Properties of atropine (5)

Back 310

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 311

Properties and uses of scopolamine (3)

Back 311

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

Front 312

Properties and uses of benzotropine (3)

Back 312

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

Front 313

Properties and uses of glycopyrrolate (3)

Back 313

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

Front 314

Properties and uses of ipratropium (3)

Back 314

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

Front 315

Properties and uses of oxybutynin (2)

Back 315

1. enters CNS but strong peripheral muscarinic blockade
2. reduces bladder urgency, spasm

Front 316

Some representative nicotinic-blocking drugs (4)

Back 316

1. hexamethonium (prototype ganglion blocker)
2. trimethaphan (ganglion blocker)
3. d-Tubocurarine
4. succinylcholine (depolarizing nicotinic blocker)

Front 317

Properties and uses of hexamethonium (3)

Back 317

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

Front 318

Properties and uses of trimethaphan

Back 318

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

Front 319

Properties and uses of d-tubocurarine

Back 319

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 320

Properties and uses of succinylcholine (4)

Back 320

1. An AGONIST
2. depolarizing neuromuscular blocker
3. very short (3-10 minutes) duration of action
4. produces neuromuscular paralysis of very short duration

Front 321

What is pralidoxime? (3)

Back 321

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 322

Examples of direct-acting sympathomimetics (4)

Back 322

1. epinephrine
2. norepinephrine
3. dopamine
4. isoproterenol

Front 323

Examples of indirect-acting sympathomimetics (4)

Back 323

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

Front 324

Actions of sypathomimetics on the CNS

Back 324

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

Front 325

Actions of sympathomimetics on eyes

Back 325

α1-activation in the pupillary dilator muscle results in mydriasis

Front 326

Actions of sympathomimetics on airways

Back 326

beta2-activation results in bronchodilation

Front 327

Actions of sympathomimetics on the GI tract

Back 327

both alpha and beta receptors mediate reduced motility

Front 328

Actions of sympathomimetics on the GU tract

Back 328

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

Front 329

Actions of sympathomimetics on the heart

Back 329

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 330

Other effects of β-receptor activation (3)

Back 330

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 (α agonists may increase strength at high doses)

Front 331

Uses of sympathomimetics (CNS)

Back 331

amphetamines are used to treat hyperkinetic attention deficit disorder and narcolepsy, and to decrease appetite

Front 332

Uses of sympathomimetics (pulmonary and cardiac) (3)

Back 332

1. epinephrine is used to treat anaphylactic shock
2. beta2 agonists (by inhalation) for acute asthmatic bronchospasm
3. beta agonists are occasionally used to increase heart rate

Front 333

Vascular uses of sympathomimetics (3)

Back 333

1. alpha 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 334

Genitourinal (GU) tract uses of sympathomimetics

Back 334

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 335

Toxicities of sympathomimetics (4)

Back 335

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 336

Give some examples of representative α-blockers

Back 336

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

Front 337

Action of α-blockers

Back 337

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 338

What is epinephrine reversal phenomenon?

Back 338

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 (mediated by α-receptors) is converted to a hypotensive response (mediated by β2 receptors)

Front 339

Norepinephrine binds to which receptors? (3)

Back 339

1. α1
2. α2
3. β1

Front 340

Epinephrine binds to which receptors?

Back 340

1. alpha1
2. alpha2
3. beta1
4. beta2

Front 341

Isoproterenol binds to which receptors? (2)

Back 341

1. β1
2. β2

Front 342

Dopamine binds to which blood vessel and heart receptors?

Back 342

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

Front 343

Phenylephrine binds to which receptors?

Back 343

1. α1
2. α2

Front 344

Albuterol binds to

Back 344

β2 receptors (it is a sympathomimetic)

Front 345

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

Back 345

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

Front 346

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

Back 346

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

Front 347

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

Back 347

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

Front 348

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

Back 348

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

Front 349

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

Back 349

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

Front 350

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

Back 350

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

Front 351

Prototype substances that bind to all α-receptors? (3)

Back 351

1. norepinephrine
2. epinephrine
3. phenylephrine

Front 352

Prototype substance that bind to α1 receptors, and its properties

Back 352

1. midodrine
2. activates Gq, increases IP3, DAG
3. smooth muscle contraction

Front 353

Prototype substance that binds to α2 receptors, and its properties (4)

Back 353

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

Front 354

Prototype substances that bind to all beta receptors (2)

Back 354

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

Front 355

Prototype substance that bind to β1 receptors

Back 355

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

Front 356

Prototype substance that binds to β2 receptors

Back 356

1. albuterol
2. activates Gs, increases cAMP
3. cardiac stimulation
4. smooth muscle relaxation
5. glycogenolysis
6. tremor

Front 357

Prototype substance that bind to β3 receptors

Back 357

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

Front 358

Prototype substance that bind to all dopamine receptors

Back 358

dopamine

Front 359

Prototype substance that binds to D1 receptors, and its properties

Back 359

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

Front 360

Prototype substance that binds to D2 receptors and its properties

Back 360

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

Front 361

Toxicities of α-blockers (3)

Back 361

1. tachycardia (all) 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 362

Prototype full antagonist beta blocker

Back 362

propranolol (stage fright, familial tremor)

Front 363

Properties of pindolol

Back 363

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

Front 364

Prototype β1-selective antagonist

Back 364

atenolol

Front 365

Mechanism of action of carvedilol (2)

Back 365

1. selective α1 antagonist
2. nonselective β antagonist

Front 366

Mechanism of action of labetalol

Back 366

1. selective α1 antagonist
2. nonselective β-antagonist

Front 367

Mechanism of action of esmolol

Back 367

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

Front 368

Define parenteral

Back 368

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

Front 369

CNS effects of beta blockers (2)

Back 369

1. sedation/lethargy
2. reduction of anxiety

Front 370

Effects of β-blockers on the eyes

Back 370

1. reduced secretion of aqueous humor
2. no significant effect on pupil or focus

Front 371

Airway effects of beta blockers

Back 371

marked bronchospasm in patients with airway disease, especially asthma

Front 372

Cardiovascular effects of beta blockers (3)

Back 372

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

Front 373

GI and GU tract effects of β-blockers

Back 373

little effect

Front 374

Other effects of β-blockers (4)

Back 374

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 375

Uses of β-blockers (5)

Back 375

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 376

define: mortality

Back 376

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

Front 377

define: morbidity

Back 377

the symptoms and/or disability resulting from a disease

Front 378

Toxicities of β-blockers (4)

Back 378

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)

Front 379

General properties of H1 blocking drugs

Back 379

1. used in treatment of hayfever and urticaria, and a few IgE-mediated allergies.
2. toxicities reflect their effects on the ANS and CNS

Front 380

General properties of H2 blocking drugs

Back 380

1. used in treatment of acid-peptic disease, especially heartburn and peptic ulcer
2. toxicities (almost exclusively cimetidine) include:
a. inhibition of hepatic CYP450
b. antiandrogenic action

Front 381

Examples of typical H2 blockers

Back 381

1. cimetidine
2. famotidine
3. nizatidine
4. ranitidine

Front 382

Examples of H3 blockers

Back 382

1. clobenpropit
2. abt-239 (nootropic)
3. ciproxifan
4. ciprilisant

Front 383

In which cells is serotonin stored?

Back 383

1. platelets
2. neurons
3. enterochromaffin cells
4. cells in the gut

Front 384

What is the main metabolite of serotonin?

Back 384

1. hydroxyindoleacetic acid (HIAA)
2. is increased in urine of patients with carcinoid tumor

Front 385

Effects of increased serotonin (and other substances) produced by carcinoid tumor include

Back 385

1. diarrhea
2. bronchospasm
3. variable changes in blood pressure
4. flushing of the skin

Front 386

Serotonin's effects are mediated by a large number of receptors, four of which are of clinical importance. Which ones?

Back 386

1. 5-HT 1D (GPCR)
2. 5-HT2 (GPCR)
3. 5-HT3 (ion channel)
4. 5-HT4 (GPCR)

Front 387

Clinical value of serotonin?

Back 387

Serotonin itself is of no value as a drug, but two more selective agonists are used:
1. 5-HT 1D (e.g., sumatriptan) for migraine. Toxicities include coronary vasospasm
2. 5-HT4 agonists (e.g., tegaserod and cisapride) increase the release of ACh in the gut--> increased motility. Toxicities include tosade de pointes arrhythmia and diarrhea.

Front 388

What is the standard treatment of migraine headache?

Back 388

1. Simple analgesics, with sumatriptan or a similar "triptan" drug, or with ergotamine
2. Prophylaxis is partially successful using propranolol, amitriptyline, calcium channel blockers, and others

Front 389

H1 receptor functions:

Back 389

1. Gq coupled
2. increased IP3 and DAG, smooth muscle contraction (EXCEPT vessels), increased secretion
3. located in smooth muscle, gland cells, some nerve endings

Front 390

H2 receptor functions:

Back 390

1. Gs coupled
2. Increased cAMP, increased acid secretion, cardiac stimulation
3. located in parietal cells (stomach) and heart

Front 391

H3 receptor functions

Back 391

1. Gi coupled
2. decreased cAMP, modulates transmitter release
3. presynaptic autoreceptor in nerve endings

Front 392

Histamine H1 antagonists can be divided into three groups. What are they? And what are their uses?

Back 392

1. First generation, older - allergy, sleep aid, motion sickness, nausea of chemotherapy
2. First generation, newer - allergy
3. Second generation - allergy

Front 393

Examples of first generation, older, H1 antagonists

Back 393

1. Diphenhydramine
2. dimenhydrinate

Front 394

Examples of first generation, newer, H1 antagonists

Back 394

1. chlorpheniramine
2. cyclizine

Front 395

Examples of second generation H1 antagonists

Back 395

1. fexofenadine
2. loratadine
3. desloratadine
4. cetrizine

Front 396

Toxicities of first generation, older antihistamines

Back 396

1. strong alpha and muscarinic block
2. strongly sedative

Front 397

Toxicities of first generation, newer antihistamines

Back 397

1. much reduced sedative and ANS effects

Front 398

Toxicities of second generation antihistamines

Back 398

negligible CNS and ANS effects

Front 399

Location and function of 5-HT1D receptors

Back 399

1. Located in neurons, perhaps other places
2. mediates increased IP3, DAG

Front 400

Location and function of 5-HT2 receptors

Back 400

1. smooth muscle, other?
2. increased IP3 and DAG, smooth muscle contraction

Front 401

Location and function of 5-HT3 receptors

Back 401

1. chemoreceptors in the central and peripheral nervous system
2. nasuea and vomiting

Front 402

Location and function of 5-HT4 receptors

Back 402

1. neurons in the gut
2. increased GI motility

Front 403

Some notes on 5-HT2 antagonists

Back 403

5-HT2 antagonists, such as ketanserin, have been developed for the treatment of carcinoid tumors. However, older drugs with overlapping effects (e.g., phenoxybenzamine [5-HT+alpha blocker] or cyproheptadine [5-HT+H1 blocker]) appear to be just as useful. In addition ketanserin has been used to treat HTN in Europe.

Front 404

Indications for 5-HT3 antagonists?

Back 404

Extremely useful antinauseants and antiemetics for patients undergoing general anesthesia or chemotherapy

Front 405

Examples of 5-HT3 antagonists

Back 405

1. ondansetron
2. granisetron
3. tropisetron
4. dolasetron

Front 406

Other serotonin related drugs

Back 406

1. ergot alkaloids (complex partial agonists at 5-Ht, alpha, and dopamine receptors)
2. ergotamine (for migraine) - natural
3. ergonovine (oxytocic agent) - natural
4. bromocriptine (used in hyperprolactinemia and parkinsonism) - semisynthetic
5. pergolide (parkinsonism) - semisynthetic
6. LSD - semisynthetic. no meidcal use, powerful hallucinogenic

Front 407

Effects and clinical uses of endogenous PGE2

Back 407

1. vasodilation, bronchodilation, oxytocic
2. oxytocic (as dinoprostone)

Front 408

Effects and clinical uses of PGE1 analog misoprostol

Back 408

1. increased bicarbonate and mucus secretion in stomach
2. prevention of NSAID-induced ulcers

Front 409

Effects and clinical uses of PGE1 analog alprostadil

Back 409

1. smooth muscle relaxation
2. erectile dysfunction

Front 410

Effects and clinical uses of endogenous PGF2alpha

Back 410

1. vasoconstriction, bronchoconstriction, oxytocic
2. no clinical uses

Front 411

Effects and clinical uses of PGF2alpha analog latanoprost

Back 411

1. increased aqueous humor drainage
2. chronic glaucoma

Front 412

Effects and clinical uses of prostacyclin (PGI2)

Back 412

1. prevents platelet aggregation, vasodilation
2. severe pulmonary hypertension (as epoprostenol)

Front 413

Effects and clinical uses of thromboxane (TXA2)

Back 413

1. facilitates platelet aggregation
2. no clinical uses

Front 414

Effects and clinical uses of LTB4

Back 414

1. leukocyte chemotaxis
2. no clinical uses

Front 415

Effects and clinical uses of LTC4

Back 415

1. bronchoconstriction
2. no clinical uses

Front 416

Effects and clinical uses of LTD4

Back 416

1. bronchoconstriction
2. no clinical uses

Front 417

Difference between NSAIDs and steroids?

Back 417

Steroids are powerful anti-inflammatory agents, whereas NSAIDs have weaker anti-inflammatory actions, but are more suitable for long-term therapy because they are less toxic

Front 418

Older NSAIDs include

Back 418

1. aspirin
2. salicylate

Front 419

Newer non-COX selective NSAIDs include

Back 419

1. indomethacin
2. ibuprofen
3. diclofenac
4. indomethacin
5. ketorolac
6. naproxen
7. piroxicam

Front 420

Selective COX-2 inhibitors include

Back 420

1. celecoxib
2. valdecoxib
3. other members of this drug

Front 421

Half-life and comments on aspirin

Back 421

1. 15 minutes (but active metabolite has a half life of 3-15 hours)
2. Widely used for pain, fever, inflammation, and antiplatelet action

Front 422

Half-life and comments on celecoxib

Back 422

1. 11 hours
2. selective COX-2 inhibitor; a sulfonamide

Front 423

Half-life and comments on diclofenac

Back 423

1. 1.1 hours
2. general use in inflammation, pain

Front 424

Half-life and comments on ibuprofen

Back 424

1. 2 hours
2. general use in inflammation, pain

Front 425

Half-life and comments on indomethacin

Back 425

1. 4-5 hours
2. general use in inflammation, pain

Front 426

Half-life and comments on ketorolac

Back 426

1. 4-10 hours
2. parenteral use in pain; an opioid substitute

Front 427

Half-life and comments on naproxen

Back 427

1. 12 hours
2. longer action

Front 428

Half-life and comments on piroxicam

Back 428

1. 20 hours
2. longest action

Front 429

Half-life and comments on salicylic acid

Back 429

1. 3-15 hours
2. active metabolite of aspirin, zero order elimination at high concentrations

Front 430

What sets aspirin apart from all other NSAIDs?

Back 430

It irreversibly blocks COX, especially in platelets. Its antiplatelet effect is, therefore, longer in duration (24-48 hrs) than its anti-inflammatory and analgesic action (4-6 hours)

Front 431

Toxicities of the NSAIDs include

Back 431

1. GI upset
2. peptic ulcers with or without bleeding
3. renal damage
4. diversion of arachidonic acid metabolism to the leukotriene pathway (may rarely present with anaphylaxis)

Front 432

Pros and cons of COX-2 selective inhibitors

Back 432

1. Pro: lower risk of GI bleeding
2. Con. increased risk of cardiovascular events (stroke and MI)

Front 433

Comments on acetaminophen

Back 433

1. similar analgesic and antiypritic effect to aspirin
2. weak COX inhibitor
3. little or no anti-inflammatory effect
4. metabolites of acetaminophen may cause hepatic necrosis (overdose)

Front 434

What is gout?

Back 434

1. chronic metabolic disease characterized by an elevated body load of uric acid.
2. manifested by depositus of urate crystals in soft tissue and joints
3. in the joints, these crystals trigger episodes of acute painful arthritis

Front 435

Which classes of drugs are used in the treatment of gout?

Back 435

1. anti-inflammatory agents (mainstay of therapy)
2. uricosuric agents (increases excretion of uric acid)
2. inhibitor of uric acid synthesis (allopurinol)

Front 436

Which anti-inflammatory drugs are are often used in the treatment of acute joint pain?

Back 436

1. ibuprofen and indomethacin
2. colcichine (highly selective for gouty arthritis) - but is usually restricted to low-dose prophylactic therapy because of GI and hepatic toxicity

Front 437

Which uricosuric agents are normally used in the treatment of gout?

Back 437

1. probenecid
2. sulfinpyrazone

They inhibit the uric acid reabsorption transporter in the straight segment of proximal tubules

Front 438

Mechanism of action of allopurinol

Back 438

1. inhibits xanthine oxidase
2. reduces concentration of insoluble uric acid
3. increases concentration of uric acid precursors, xanthine and hypoxanthine

Front 439

Clinical correlations on the treatment of gout

Back 439

1. acute attacks require strong anti-inflammatory drugs, strong analgesics, or both
2. indomethacin and ketorolac are often used. ketorolac may be used parenterally
3. uricosurics may precipitate an immediate attack and should always be used in conjunction with colcichine or other agents initially
4. allopurinol's benefits are slow in onset and are suitable only for long-term therapy

Front 440

In addition to the obvious cardiovascular events that hypertriglyceridemia may cause, it may also contribute to an incresed risk of

Back 440

acute pancreatitis

Front 441

Drugs used in hypercholesterolemia include

Back 441

1. statins
2. resins
3. ezetimibe
4. niacin
5. fibrates

Front 442

Mechanism of action of statins

Back 442

(e.g., levostatin and atorvastatin)
1. inhibitors of cholesterol synthesis (HMG-CoA reductase inhbitors)
2. reduced cholesterol concentrtion results in increased LDL-binding receptors on liver cells, which increases clearance of LDL from blood
3. most statins only reduce cholesterol, but atorvastatin reduces both cholesterol and triglyceride levels

Front 443

Mechanism of action of resins

Back 443

(e.g., cholestyramine and colestipol)
1. nonabsorbable macromolecules, bind to and prevent reabsorption of cholesterol and bile acids
2. resins tend to increase triglycerides

Front 444

Mechanism of action of exetimibe

Back 444

new drug that reduces the absorption of cholesterol from the intestines, the exact mechanism is unknown

Front 445

Mechanism of action of niacin

Back 445

(nicotinic acid and vitamin b3)
1. the exact mechanism is not fully understood.
2. high doses cause a decrease in secretion of VLDL from the liver into blood, and thus decreased LDL.
3. is also effective in hypertriglyceridemia and may cause increase in HDL

Front 446

Mechanism of action of the fibrates

Back 446

(e.g., gemfibrozil and fenofibrate)
1. activate peroxisome proliferator-activator receptor alpha (PPAR-a)
2. increases synthesis of lipoprotein lipase and other enzymes
3. serum triglyceride concentrations are reduced, may be a reduction in LDL

Front 447

Toxicities of statins

Back 447

1. may cause serious skeletal muscle or liver damage
2. may interfere with myelination in growing infants.

These drugs are contraindicated in pregnancy

Front 448

Toxicities of niacin

Back 448

1. high doses causes a transient uncomfortable flushing with itching (may be reduced with aspirin)
2. may rarely cause elevation of:
a. liver enzymes
b. hyperuricemia
c. glucose intolerance

Front 449

Toxicities of resins

Back 449

1. unpleasant gritty taste
2. may cause GI discomfort (including bloating and constipation)
3. impaired fat-soluble vitamin and drug absorption

Should be avoided in hypertriglyceridemia

Front 450

Toxicities of fibrates

Back 450

1. nausea
2. skin rash
3. increased effect of antiplatelet drugs
4. increased risk of gall stones

Front 451

Anticoagulants include

Back 451

1. warfarin (oral; blocks reactivation of vitamin K epoxide; monitor with PT and INR)
2. heparin (parenterally, binds factor Xa and AT III)

Front 452

Heparin is available in both HMW and LMW forms. The differences

Back 452

1. HMW - binds Xa and AT III. AT III in this bound form is activated 1000-fold --> immediate clotting inhibition. The response is variable, must monitor.
b. LMW - inhibit factor Xa, but less effect on AT III. Response is predictable and so does not require monitoring.

Front 453

Examples of LMW heparins

Back 453

1. enoxaparin
2. dalteparin

Front 454

Major clinical application of heparins and warfarin are

Back 454

in the prevention and treatment of venous clotting, especially DVT

Front 455

Toxicities of heparins and warfarin

Back 455

1. bleeding
2. warfarin is a teratogen
3. heparin causes dose-dependent thrombocytopenia, but occasionally causes a more severe loss of platelets

Front 456

Most important antiplatelet drugs include

Back 456

1. aspirin
2. clopidogrel - blocks ADP receptor on platelets
3. ticlopidine - blocks ADP receptor on platelets
4. fiban drugs (eptifibatide and tirofiban) - IIb/IIIa blocker
5. abciximab - IIb/IIIa blocker

Front 457

Most important clinical use of fibrinolytics

Back 457

intravenous administration for pulmonary embolism and myocardial infarction

Front 458

Most important fibrinolytic drugs

Back 458

1. streptokinase - may cause allergic response, bleeding
2. alteplase (tPA), reteplase - bleeding
3. urokinase - bleeding

Front 459

Anemia results from

Back 459

1. inadequate dietary iron
2. inadequate vitamin intake
3. inadequate RBC production
4. accelerated RBC breakdown

Front 460

What is anemia?

Back 460

a deficiency of red blood cells (RBCs) or hemoglobin

Front 461

For simple iron deficiency anemia, oral supplementation is effective. In what form is iron given?

Back 461

1. ferrous sulfate
2. ferrous gluconate

ferric iron salts are poorly absorbed

Front 462

Iron is irritating to the stomach, annd some patients cannot tolerate the doses required for rapid correction of severe deficiency. What options do these patients have?

Back 462

1. iron dextran
2. iron sucrose complex
3. iron gluconate complex

all parenteral iron

Front 463

Manifestations of iron poisoning include

Back 463

1. vomiting
2. abdominal pain
3. diarrhea
3. necrotizing enteritis, followed by shock, lethargy, metabolic acidosis, death

Front 464

How do you treat iron poisoning?

Back 464

Prompt diagnosis and an iron chelator, such as deferoxamine

Front 465

Growth factor used for anemia

Back 465

1. epoetin (human recombinant erythropoietin)
2. increases RBC production
3. may cause HTN, thrombotic events

Front 466

Growth factor used for granulocytopenia (F)

Back 466

1. filgrastim (human recombinant GM-CSF)
2. increases neutrophil production
3. may cause bone pain

Front 467

Growth factor used for granulocytopenia (S)

Back 467

1. sargramostim (human recombinant G-CSF)
2. stimulates most marrow precursors, but increases neutrophil production the most
3. may cause fever, myalgia, peripheral and pulmonary edema

Front 468

Growth factors used for thrombocytopenia

Back 468

1. oprelvekin (human recombinant IL-11)
2. stimulates platelet production
3. may cause fatigue, headache, dizziness

Front 469

Definition of asthma

Back 469

asthma is a chronic inflammtory airway disease, with superimposed transient episodes of bronchoconstriction

Front 470

Therapy of asthma consists of

Back 470

1. bronchodilators - control of symptoms
2. anti-inflammatory drugs - prophylaxis

Front 471

Bronchoconstriction in asthma is mediated mostly by

Back 471

1. leukotrienes
2. other smooth muscle activators from mast cells and eosinophils in the airways

Front 472

Bronchodilators consist of

Back 472

1. beta2-selective agonists
2. muscarinic blockers
3. theophylline

Front 473

Drug of choice in acute episodes of asthmatic bronchoconstriction

Back 473

1. beta2-selective agonists, such as:
a. albuterol
b. metaproterenol
2. they are physiologic leukotriene antagonists (and others increasing cAMP)
3.

Front 474

Toxicities of beta2-selective agonists

Back 474

1. tremor
2. tachycardia

However, do not limit the drug during an acute attack: uncontrolled bronchoconstriction can be fatal

Front 475

The most important muscarinic antagonists used in asthma are atropinelike. Their names are

Back 475

1. ipratropium
2. tiotropium

*not as effective as SABAs

Front 476

Toxicities of ipratropium and tiotropium

Back 476

1. dry mouth
2. tachycardia (rarely)
3. cycloplegia (rarely)

Front 477

Toxicities of theophylline include

Back 477

1. GI disturbances
2. tremor
3. arrhythmias
4. convulsions

Front 478

Third kind of bronchodilator

Back 478

1. theophylline - is related to caffeine and theobromine, but more effective than either
2. inhibits phosphodiesterase -->increased levels of cAMP
3. not active when inhaled

Front 479

Which anti-inflammatory drugs are used in asthma?

Back 479

1. corticosteroids
2. mast cell stabilizers
3. leukotriene antagonists

Front 480

Most important prophylactic agent for asthma

Back 480

corticosteroids - given by metered-dose inhaler when possible

Front 481

Which steroids are most commonly used in asthma?

Back 481

1. beclomethasone
2. fluticasone
3. uhm... others...

Front 482

How do corticosteroids help in asthma?

Back 482

inhibit leukotriene and inflammatory cytokine production and release

Front 483

Toxicities of inhaled corticosteroids include

Back 483

1. temporary retardation of growth young children
2. candidal yeast infection of larynx

Front 484

Mast cell stabilizers used in asthma include

Back 484

1. cromolyn
2. nedocromil

highly insoluble compounds that can be administered by metered-dose inhalation with practically no systemic toxicity

Front 485

How do mast cell stabilizers work?

Back 485

Probably by inhibiting mast cell release of inflammatory and allergic mediators, including leukotrienes, cytokines, and histamine

Front 486

Leukotriene receptor antagonists used in asthma

Back 486

1. zafirlukast
2. montelukast

orally active (advantageous in young children and others who can't use inhalers)

Front 487

Downside of leukotriene receptor antagonists?

Back 487

1. not as effective as corticosteroids
2. no value in acute bronchospasm

Front 488

Physostigmine and bethanechol in small doses have similar effects on all of the following

Back 488

1. salivary glands
2. ureteral tone
3. sweat glands
4. gastric secretion

Front 489

Insecticidal activity of parathion (4)

Back 489

1. indirectly acts on acetylcholinesterase; ingested-> oxidized to paraoxon
2. paraoxon is the most potent acetylcholinesterase inhibitory insecticide used
3. about 70% as potent as sarin
4. easily absorbed through skin

Front 490

Parathion has all of the following characteristics (4)

Back 490

1. less persistent in the environment than DDT
2. more toxic to humans than malathion
3. very lipid soluble and easily absorbed through skin and lungs
4. its toxicity, if treated early, may be partially reversed by pralidoxime

Front 491

In the treatment of myasthenia gravis, the best agent for distinguishing between myasthenic crisis (insufficient therapy) and cholinergic crisis (excessive therapy) is

Back 491

1. edrophonium
2. in myasthenia gravis the patient's muscle strength will increase due to more availible acetylcholine
3. in a cholinergic crisis, the weakness will worsen due to induction of a depolarizing block

Front 492

The cause of death in nerve gas poisoning is usually

Back 492

asphyxiation