Mechanisms 1 - Midterm Flashcards

Front 1

What is chemical antagonism?

Back 1

- chemical interaction between two drug molecules
- ex. chelation acid/base interaction, use of antacid which neutralizes drug.

Front 2

What is physical antagonism?

Back 2

- Physiological antagonism - two drugs that produce opposite effects through separate receptors
- NE - B1 → ↑ heart rate
- AcH - Muscarinic → ↓ heart rate

Front 3

What is pharmacological antagonism?

Back 3

Interaction at same receptor. Competitive & noncompetitive antagonism?

Front 4

What is competitive antagonism?

Back 4

- two drugs that act at the same site
- both act reversibly
- antagonist effects can be overcome by ↑ dose of agonist

Front 5

What is noncompetitive antagonism?

Back 5

- effects occur on the same receptor or a separate but related receptor
- binding can be reversible or irreversible
- can not overcome antagonist by ↑ dose of agonist

Front 6

What is potency?

Back 6

• biological activity of drug per unit weight
• efficacy doesn’t tell much about potency
• not a useful term from pharmacological standpoint

Front 7

What is a partial agonist?

Back 7

• agonist that CANNOT produce a max response
• reduced efficacy compared to full agonist; does not deal with affinity

Front 8

What kinds of drugs are receptors NOT involved?

Back 8

• antacids - undergo chemical reaction
• osmotic diuretics
• chelaters - chelate iron or other metals; interaction between two drug molecules
• incorporation of drug molecule into DNA or RNA (anti-cancer drugs)

Front 9

What are the 2 types of drug effects?

Back 9

• graded or continuous response - eg. can affect bp to certain point where can get an effect on heart rate, body temperature
• quantal, All-or-None Response, not graded. ie. death, seizure, vomiting

Front 10

What is synergism?

Back 10

Response of drugs A + B is greater than the algebraic sum.

Front 11

What is potentiation?

Back 11

The addition of drug B to drug A makes A more potent (a smaller dose of A required to generate response).

Front 12

What is antagonism?

Back 12

The response of drugs A + B is less than the algebraic sum.

Front 13

What is the measure of theraputic index?

Back 13

LD50/ED50 Larger theraputic index = worse

Front 14

What is the measure of certain safety factor?

Back 14

LD1/ED99

Front 15

What are pharmacogenetics?

Back 15

- influence of genetics -or- inherited tendencies on drug effects
• idiosyncracy - genetically determined abnormal response to a drug.
• iatrogenic - someone made a mistake - wrong drug prescribed - pt gets bad rxn to drug (human error)
*allergic reactions are not idiosyncracies

Front 16

What is the placebo effect?

Back 16

There can be a measured effect: when the person takes a drug, there is a release of enkephalins or psychological effects towards improvement.

Front 17

What are the characteristics of the somatic nervous system?

Back 17

- Arise from efferent branch of the PNS.
- Located all along spinal cord.
- No intermediate ganglia.
-Synapses are myelinated.
- Innervated byskeletal muscle - neuromuscular junction (NMJ)
- Activity: always excitatory; muscle is dependent on stimulation to contract.

Front 18

What are some characteristics of the autonomic nervous system?

Back 18

- Branch from the efferent PNS
- Arise from restricted areas
- Intermediate autonomic ganglia
- Synapses: preganglionic - myelinated postganglionic - nonmyelinated
- Innervated by smooth muscle, cardiac muscle, glands, neuroeffector junction (NEJ)
- Actions: excitatory, inhibitory - muscle/glands that have autonomous activity

Front 19

What are the characteristics of the PNS?

Back 19

- cranio/sacral regions (top & bottom of spinal cord)
- long preganglionic
- short postganglionic
- ganglia near target organ
- low degree of divergence
-- control over small area
- localized effects
- internal housekeeping dominant at times of quiet or rest (discreet control)

Front 20

What are the characteristics of the CNS?

Back 20

- thoracolumbar regions
- short preganglionic
- long postganglionic
- ganglia near spinal cord
- high degree of divergence
-- influences large area of muscle
- widespread effects
- answer to external challenges like stress

Front 21

What are the effects of dual innervation on the heart?

Back 21

- SNS works on B1 receptors to increase HR
- PNS works on muscarinic receptros to decrease HR

Front 22

What are the effects of dual innervation on the GI tract?

Back 22

- SNS decreases GI motility, B2 receptors relax, A receptors contract.
- PNS increases GI motility, increase contractions, muscarinic receptors relax sphincters

Front 23

What are the effects of dual innervation in the iris?

Back 23

- CNS contracts radial muscles, causing mydriasis
- PNS acts on circular muscles, causing miosis.

Front 24

How do the effects of dual innervation present in the body?

Back 24

- Normal innervated heart rate = 70 bpm
- denervated heart rate = 100-120 bpm
- dominant tone PNS
- PNS dominates except on blood vessels & sweat glands

Front 25

What do botulinum toxin and black widow toxin do in the body?

Back 25

- Botulinum toxin: blocks exocytosis process of acetylcholine on cholinergic synapse.
- Black widow spider toxin: increases exocytosis of acetylcholine on cholinergic synapses.

Front 26

What is acetylcholinesterase?

Back 26

Terminates action of ACh, primarily located in nerve terminals (cholinergic nerve terminals). (Target for anticholinesterase)

Front 27

What is butyro cholinesterase?

Back 27

aka "serum cholinesterase" "pseudo cholinesterase," no butyro choline in the body.

Front 28

What is serum cholinesterase?

Back 28

In liver, kidney, blood. Prevents you from having circulating acetyl cholinesterase.

Front 29

What are the types of muscarinic receptors?

Back 29

- M1: CNS (in most cases), involved in IP3/DAG channel
- M2: Peripheral (some CNS) - more significant in the heart, involved in K+ channel, increase cAMP
- M3: Peripheral (some CNS) - general receptors located on glands, smooth muscle, increases IP3/DAG
- Having these receptors separate is not important at this point, we cannot yet select between the 3 types.

Front 30

What are parasympathomimetic drugs?

Back 30

Drugs that have affinity and efficacy on muscarinic receptors.

Front 31

What are the functions of parasympathomimetic drugs?

Back 31

1. Cause a decrease in heart rate (M2 receptor)
2. Increase in GI motility.
3. Increase in urination
4. Pupils contract (meiosis)
5. Increase in salivation & increase in gastric acid secretion
6. Increase in lacrimation
7. Bronchial secretions
8. Increase in sweating (sympathetic cholinergic response).
9. Hypotension

Front 32

What happens at the cholinergic synapse?

Back 32

• On pre-synaptic membrane have transporter that transport choline into pre-synapatic neuron
• Choline + AcetylCoA gives ACh by acetyl transferase
• Depolarization (Ca++ influx due to open of gated Ca++ channels), triggers release of ACh (exocytosis – 6 process involved)
• ACh crosses synapse and find to receptor site (nicotinic/musconic), triggers depolarization or second messenger activation in the pre-synaptic neuron
• ACh then gets broken down into choline (retaken up into pre-synaptic neuron) and acetate by acetylcholinesterase (“true” -found at the synapse attached to outside of cell facing synapse) / pseudo-cholinesterase (“butyro”/”serum” – not located at the synaptic clef, its found mostly in blood, also kidney and liver, don’t know exactly why its there, break down ACh that escape acetylcholinesterase so there is NO circulating ACh)

Front 33

What are the properties of bethanechol?

Back 33

* Parasympathomimetic, muscarinic agonist
-resistant to cholinesterase
-Minimal nicotinic activity
-Selecting GI urinary tract, used to stimulate urination
-Used postoperatively, postpartum, atany of the GI tract or urinary bladder
-Must be used in situations that are non-obstructive
-Contraindications: bronchial asthma, gastric/peptic ulcers, cardiac insufficiency, hyperthyroidism (produces atrial fibrillation).
-Given orally. Never given by injection.
- If give bethanechol via IV → major drop of BP (hypotension) b/c there are muscarinic receptors in vessels → stimulated relaxes → dilation (almost never stimulated since they are not innervated plus there is normally no circulating ACh, except when given in large dose as drug)

Front 34

Why isn't acetylcholine used as drug therapy?

Back 34

It is not selective (work on both nicotinic and muscarinic receptors) and can’t use systematically because it will be hydrolyze immediately, destroyed in stomach before it reaches systemic

Front 35

What is pilocarpine used for?

Back 35

Used in glaucoma to reduce pressure, induce miosis.

Front 36

What are cholinesterase inhibitors?

Back 36

- indirect-acting (don’t act directly on the receptor)
- do NOT have affinity or efficacy for cholinergic receptors
- 2 classes: reversible vs. irreversible

Front 37

What is physostigmine?

Back 37

* reversible cholinesterase inhibitor
- Tertiary amine - can enter CNS - 10,000 times greater affinity for cholinesterase than Ach.
○ Has only indirect cholinomimetic effects
○ Indicated for glaucoma, rarely used for GI/urinary atony.
- Used for poisonings by agents such as atropine.
- occupies active site of cholinerterase, blocks the degradation/break down of ACh, increase ACh at synapse as well as allow some circulating ACh to happen
- see an increase in normal PSNS activity (won’t see hypotension initially), increase sweating
- affects neuromuscular junction, increase in skeletal muscle contractions (fasciculations [twitches] – early effect)
- ganglionic stimulation (at high doses)

Front 38

What is neostigmine?

Back 38

* reversible cholinesterase inhibitor
- (quaternary amine has positive charge), doesn’t cross blood brain barrier, NO CNS activity
- Small amount of direct action on cholinergic receptors
- Indications: glaucoma (to decrease pressure in eye by contracting pupil) and post-op/post-partum/atony of GI-urinary tracts and myasternia gravis (condition where people develop antibodies to nicotinic receptors in the skeletal muscle and need more ACh, produce desired effects
- Neostigmine and other non-CNS acting reversible anti-cholinesterases are really good for myasternia gravis

Front 39

What are irreversible types of cholinesterase inhibitors used for?

Back 39

toxicologic interest, mainly used as pesticides (very toxic) and nerve gases

Front 40

What are some treatments for exposure to neostigmine?

Back 40

○ Atropine
○ Artificial respiration (may have to be for days).
○ Pralidoxine (2-PAM)

Front 41

What are organophosphates (w/ F-phosphorous group)?

Back 41

- ChE – cholinesterase has anionic site of glu-COOH and extoratic site of ser-OH
- F of organophosphates gets cleaved off and organophosphate binds covalently at extoratic site → initially its relatively irreversible but as time goes on → lose R1 group (aging) → completely irreversible
- ACh has to bind to both anionic and extoratic site → with extoratic site blocked → no ACh cleavage
- Requires days/weeks to get back to normal activity by making new ChE

Front 42

What is DFP?

Back 42

*diisopropylflurophospate, an irreversible cholinesterase inhibitor
- Is a poisonous insecticide
- exaggerated PSNS activity (lots of salivation)
- fasciculations (twitching)
- tightness in chest (decrease contraction of diaphragm)
- flaccid paralysis of skeletal muscle (due to muscle fatigue after spasm)
- respiratory paralysis & death
- Sometimes a treatment for glaucoma

Front 43

What is malathione?

Back 43

*irreversible cholinesterase inhibitor, pesticide
- not organophosphate but gets converted to one by body (malaoxone) but is quickly inactivated by body in human but insects cannot inactivate it, makes good insecticide

Front 44

What are the functions of parasympathomimetic drugs?

Back 44

1. Cause a decrease in heart rate (M2 receptor)
2. Increase in GI motility.
3. Increase in urination
4. Pupils contract (meiosis)
5. Increase in salivation & increase in gastric acid secretion
6. Increase in lacrimation
7. Bronchial secretions
8. Increase in sweating (sympathetic cholinergic response).
9. Hypotension

Front 45

What happens at the cholinergic synapse?

Back 45

• On pre-synaptic membrane have transporter that transport choline into pre-synapatic neuron
• Choline + AcetylCoA gives ACh by acetyl transferase
• Depolarization (Ca++ influx due to open of gated Ca++ channels), triggers release of ACh (exocytosis – 6 process involved)
• ACh crosses synapse and find to receptor site (nicotinic/musconic), triggers depolarization or second messenger activation in the pre-synaptic neuron
• ACh then gets broken down into choline (retaken up into pre-synaptic neuron) and acetate by acetylcholinesterase (“true” -found at the synapse attached to outside of cell facing synapse) / pseudo-cholinesterase (“butyro”/”serum” – not located at the synaptic clef, its found mostly in blood, also kidney and liver, don’t know exactly why its there, break down ACh that escape acetylcholinesterase so there is NO circulating ACh)

Front 46

What are the properties of bethanechol?

Back 46

* Parasympathomimetic, muscarinic agonist
○ resistant to cholinesterase
○ Minimal nicotinic activity
○ Selecting GI urinary tract, used to stimulate urination
○ Used postoperatively, postpartum, atany of the GI tract or urinary bladder
○ Must be used in situations that are non-obstructive
○ Contraindications: bronchial asthma, gastric/peptic ulcers, cardiac insufficiency, hyperthyroidism (produces atrial fibrillation).
○ Given orally. Never given by injection.

Front 47

Why isn't acetylcholine used as drug therapy?

Back 47

It is not selective (work on both nicotinic and muscarinic receptors) and can’t use systematically because it will be hydrolyze immediately, destroyed in stomach before it reaches systemic

Front 48

What are muscarinic antagonists?

Back 48

• has affinity but NO efficacy at muscarinic receptor
• all are competitive and reversible
• decrease in PSNS responses
• order of sensitivity/inhibition as dose/time increase
- decrease sweating (raise body temp) (exception – SNS response but mediated by ACh) [at very high doses decrease salivation (dry mouth) (M3)
- mydriasis, dilate eye, lose near vision (loss of accommodation – cycloplegia) and increase in heart rate (M2 receptors) due to decrease vagal input in the heart (but sometimes have vagal stimulation then vagal blockage)
- Inhibition of GI tone and inhibition of urinary tract
- Inhibition of GI secretions (especially acid secretion)
- CNS effects: excitation, delirium, hallucinations, and convulsions & coma (really severe cases) atropine b/c it crosses the BBB
- Nicotinic blockade, block ganglionic and skeletal muscles leading to respiratory paralysis

Front 49

What is atropine?

Back 49

*muscarinic antagonist
- hyoscyamine (belladonna alkaloid) cross BBB and CNS stimulant
- GI antispasmotic
- Pre-anesthetic, dry up secretions which can build up w/ anesthetic
- Most commonly used in cardiovascular disease to increase HR in slow HR due to excess vagal tone

Front 50

What is scopalamine?

Back 50

- hyoscine (also a belladonna alkaloid)
- like atropine EXCEPT it is a CNS depressant (not stimulant) and it decreases motion sickness
- twilight sleep, drowsiness (used as a truth serum before)
- mainly used as a pre-anesthetic agent to decrease secretions and drowsiness
- anti-emetic effect (nausea from motion sickness prophylactic)
- not good for ppl on chemotherapy

Front 51

What are the quaternary amine muscarinic antagonists?

Back 51

• Quaternary amines – synthetics (doesn’t cross BBB), peptic ulcers/IBS w/o CNS side effects to decrease GI motility and decrease acid secretions (but still have all other side effects as well as some ganglionic blockade effect, orthostatic hypotension)
- propantheline
- clidinium

Front 52

What are the muscarinic antagonists used to induce mydriasis?

Back 52

- topical administration to eye, block circular muscle
- enlarge pupil (no near vision), all produce cycloplegia (can’t adjust for near and far vision)
- Homatropine
- Cyclopentolate
- Tropicamide

Front 53

What are the functons of ganglionic stimulants?

Back 53

o augments the dominant tone which ↑ parasympathetic stimulation
o exception: may ↑ or ↓ heart rate
1. GI motility ↑
2. urinary tract motility ↑
3. blood pressure can go up or down: it is unpredictable
4. sympathetic stimulation leading to vasoconstriction

Front 54

What do ganglionic blockades do?

Back 54

o everses/removes dominant tone and nondominate tone (parasympathetic and sympathetic respectively); ganglionic blocker drug blocks both SNS and PNS
o the reason why we think it looks like sympathetic controlling is because the ratio of blocking parasympathetic is greater than sympathetic. Recall that when we remove both parasympathetic and sympathetic tone in a system, what we have left is the intrinsic rhythm.
1. GI tract: if parasympathetic blocked (dominant tone), then constipation results
2. Urination: if parasympathetic blocked (dominant tone), then you will get urinary retention
3. Blood vessels: dominant tone is sympathetic. If given ganglionic blocker drug, both SNS and PNS inhibited. However the dominant tone is blocked more, therefore we will see vasodilation.
4. Heart rate: dominant tone is parasympathetic. If it is removed, we will see tachycardia or increased heart rate.

Front 55

What is Mecamylamine?

Back 55

* ganglionic blocker
- reversal of dominant "autonomic tone"
- many side effects: GI, urinary retention, pupils
- used to treat severe hypertension, only used as 3rd or 4th line agent
- 4. orthostatic hypotension or postural hypotension - when reclining, there is adequate blood flow. Upon standing, there is a shift or pooling of blood in lower extremities. Lack of blood flow thru brain - light headed, faint

Front 56

Where does nicotine work?

Back 56

Works on both NN & NM receptors, is a ganglionic stimulant & ganglionic blockade

Front 57

What are competitive antagonists of somatic receptors on the NMJ?

Back 57

Somatic receptors: Nicotinic receptors on SKM (NM)
- Neuromuscular blockers cause paralysis. They are used in surgical procedures where a respirator needs to be kept around.
- Competitive Antagonists
- Curare-like (one of the first drugs that blocked NMJ - used in arrows)
All quaternary:
• Pancuronium Bromide
• Vecuronium - no CNS effects
• Rocuronium
- Block reversibly (competitive) NM at the NMJ
• results in muscle paralysis
• affects fast twitch muscles the fastest
• last muscle paralyzed is the diaphragm which has a large number of spare receptors to maintain contraction

Front 58

What is the depolarizing agent on somatic receptors on the NMJ?

Back 58

- Depolarizing Agents
(quaternary structure)
- Succinylcholine - continuous infusion (DOA = 3-4 minutes)
- MOA - 2 phases of activity
- Phase 1: direct depolarization of SKM through activation of NM receptors. See fasciculations because it first acts like an agonist. After 2 minutes, you end up with muscle relaxation/paralysis.
- Phase 2: gradual depolarization of muscle, BUT it is not responsive to AcH. This is the desensitization phase. As soon as succinylcholine is removed, you go back to normal.

Front 59

What are the characteristics of the competitive antagonists of somatic receptors on the NMJ?

Back 59

- causes respiratory paralysis
- no CNS effects
- few side effects
- onset of action (IV) 1-2 min
- duration of action 30-60 min
- induce recovery by giving anticholinesterase (neostigmine), increasing ACh to overcome effects

Front 60

What are the characteristics of the depolarizing agents of somatic receptors on the NMJ?

Back 60

- causes respiratory paralysis
- osa 20-30 seconds
- doa 2-5 minutes
(serum chE metabolizes succinylcholine)
- no CNS effects
- ↑ intraocular pressure
- produce muscular contractions (soreness)
- release of K+ (can lead to arrythmias)
- prolonged apnea (some people may have abnormal pseudo-chE). This is idiosyncratic.
- Not competitive
DO NOT use anticholinesterase, block break down of succinylocholine and increase of ACh doesn’t help
- Effects of succinylcholine are prolonged by anti-cholinesterases
- Interaction with halothane, causes malignant hypothermia

Front 61

How is tyrosine transported in the presynaptic node?

Back 61

In the presynaptic node Tyrosine transported in → tyrosine hydroxylase → dopa → dopa decarboxylase → dopamine (packaged in a vesicle) → DBH → norepinephrine (norepi in cytoplasm can negative feedback and shut down norephiphrine synthesis

Front 62

Where can PNMT convert norepi to epi?

Back 62

In the adrenal medulla.

Front 63

What are some mechanisms of norepi?

Back 63

- Norepi can act on post-synaptic receptors (glands/smooth muscles/vessels), alpha 1, beta 1, beta 2 (beta 3)
- Norepi can go to alpha 2 receptor (pre-synaptic), negative feedback, decrease Norepi production
- Norepi can be metabolized or reuptake actively back into the synapse

Front 64

What is the key to getting rid of norepi?

Back 64

- Reuptake (90% of norepi)

Front 65

What are catecholamines metabolized by?

Back 65

• catecholamine metabolized by monoamine oxidases (MAO) and catechole-O-methyl transferase (COMT)

Front 66

What is MAO-A?

Back 66

- MAO-A norepi and serotonin as preferred substrates (epi)
• Only form in the placenta and GI
• Predominant form in the peripheral SNS
- in brain/liver

Front 67

What is MAO-B?

Back 67

- MAO-B, dopamine is preferred substrates (epi)
• Only form in the platelets
• MAO-B inhibitor used for Parkinson’s disease
- in brain/liver

Front 68

What is COMT?

Back 68

- cytoplasmic soluble
- highest level in liver and kidney
- not high/present in nervous system, not really in nerves
- works on diet/circulating catecholamines b/c of reuptake in liver and kidney cells as well

Front 69

What are the actions of norepi?

Back 69

• Levarterenol (generic name for norepinephrine), only one therapeutic use as a vasopressor (increase blood pressure) not used because there are many side effects and not orally effective (only given IV b/c of high metabolism)
- given IV, BP due to peripheral resistance, raised both systolic and diastolic pressure, mean blood pressure increased
- alpha 1, alpha 2, beta 1 agonist
- decrease in HR b/c of reflex bradycardia (activates vagus and sends vagal tone to decrease HR)
- NO change in cardiac output, not effective drug, puts more stress in heart

Front 70

What are the functions of epi?

Back 70

- alpha 1, alpha 2, beta 1 and beta 2 agonist
- not effective orally, inhalation and mostly IV/injection
- IV: average BP have little change (because have vasodilation and vasoconstriction) but increase in pulse pressure (difference b/w systolic and diastolic pressure)
- Alpha 1 receptors in skin, GI mucosa, GI tract
- Beta 2 receptors in skeletal muscle, liver, and heart
- Shunting of blood away from skin and GI to liver (glucose), skeletal muscle and heart
- Used for cardiac stimulant (activate heart when it stops), bronchodilator (asthma), anaphylaxis (b/c of bronchovasodilatation, shock, epi reverse this)
- Increase HR due to beta 1 response because no change in BP, Increase cardiac output

Front 71

What are the characteristics of alpha-1 receptors?

Back 71

- Usually excitatory
- Works on smooth muscle
- Contracts radial muscles in eye
- Contracts sphincters in GI tracts and urinary tract
- Piloerection – contract at the base of hair (Goosebumps)
- Vasoconstriction of blood vessels
- Contracts the uterus (more receptors at time of labor)
- Pancreas effects on acinar cells - decrease in secretion of acinar cells (digestive enzymes)

Front 72

What are the characteristics of alpha-2 receptors?

Back 72

- Primarily pre-synaptic
- Inhibit release of norepi, epi and dopamine
(Also ACh)
- Inhibit insulin by stimulating pancreatic beta cells
- Cause platelet aggregation

Front 73

What are the characteristics of beta-1 receptors?

Back 73

- Mostly in heart
- Excitatory
- Increase heart rate
- Increase conduct velocity
- Increase automaticity
- Increase force of contraction
- In Kidney – stimulate release of renin
- Renin/angiotensin, giving vasoconstriction

Front 74

What are the characteristics of beta-2 receptors?

Back 74

- Inhibitatory (exception in liver)
- Inhibit smooth muscle contraction in bronchioles
- Bronchodilator, Vasodilator
- GI – inhibits contraction of smooth muscle
- Relax uterus (decrease in receptors during labor)
- In liver: increase glycogenolysis and gluconeogenesis
- Increase blood glucose
- In Pancreas, Beta cells increase insulin

Front 75

What are characteristics of DA (dopamine) receptors?

Back 75

- D1 (renal vasculature)
- vasodilate renal blood vessels (tx of shock)

Front 76

What do beta 3 receptors do?

Back 76

Increase lipolysis

Front 77

What is isoproterenol?

Back 77

*catecholamine, sympathomimetic
- beta1, beta2 agonist, metabolized by COMT, causes vasodilation, significant increase in HR, beta 1 effect and tachycardia
- main therapeutic use bronchodilator and cardiac stimulant

Front 78

What is dobutamine?

Back 78

*catecholamine, sympathomimetic
- selective beta1 agonist (not orally effective, given via IV as cardiac stimulant)
- cardiac failure, ICU, short term management (lose effectiveness over 1 day because of down-regulation of beta1 receptors)
- this is not a naturally occurring compound

Front 79

What is dopamine used for?

Back 79

*catecholamine, sympathomimetic
- D1 receptors and other DA (dopamine) receptor agonist
- therapeutic use targets D1 receptors for peripheral use (given via IV)
- also conversion of DA to norepi and epi
- used to manage shock, D1 vasoconstricts most vascular beds EXCEPT renal vasculature where D1 vasodilate to prevent kidney failure by MAINTAINING renal blood flow (doesn’t vasoconstrict heart or brain)
- If give too much, norepi vasoconstricts renal blood flow

Front 80

How is tyramine an indirect-acting sympathomimetic?

Back 80

- displaces norepi from vesicles for a peripheral effect
• Not effective orally
• Significant increase of BP (2-3 mins) after one injection, 4-5, 10-12 shots once after another, BP increase is less after each shots, tachyphylaxis (rapid development of tolerance) due to depletion of norepi stores
• Don’t use therapeutically but it is in wines, aged cheeses, salami

Front 81

What are the effects of amphetamine?

Back 81

*indirect-acting sympathomimetic
- works on CNS (central) and PNS (peripheral)

Front 82

What are the effects of ephedrine?

Back 82

*indirect-acting sympathomimetic
- releases norepi and some direct beta 2 agonist effect

Front 83

What are the effects of pseudoephedrine?

Back 83

*indirect-acting sympathomimetic
- just a releaser, no direct beta 2 effect

Front 84

What is reserpine?

Back 84

*indirect-acting sympathomimetic
- norepi releaser plus blocks uptake at vesicle level (only drug that leads to long term depletion (several days) of norepi, epi, serotonin, DA and histamine.
- Has central and peripheral effect, antihypertensive and antipsychotic drugs (but not really used now)

Front 85

How does cocaine act as an indirect-acting sympathomimetic?

Back 85

- blocks reuptake of norepi, DA and serotonin
• Norepi has greater and longer effect w/ cocaine use
• Tyramine doesn’t have any effect w/ cocaine use because it can’t get into the neuron since reuptake transporter is blocked
• Tricyclic antidepressant
• DDI

Front 86

What is Tranylcypromine?

Back 86

- gets into nerve endings and block MAO, have lots of potential interactions because MAO is not just in the nerve endings (MAO in mitochondria of nerve cells, liver, GI tract and platelets
• Tyr (tyramine): via food doesn’t get pass GI because MAO in GI metabolize it
• With tranylcypromine, blocks MAO, Tyr gets absorbed, releases norepi, hypertensive reaction
• Used therapeutically as anti-depressant to stimulate brain

Front 87

What do alpha agonists do?

Back 87

- alpha 1, alpha 2 receptors - VASOCONSTRICTION
• Therapeutic uses:
- Hypotension- not agent of choice because also vasoconstrict kidney beds
- Nasal decongestant: vasoconstrict vascular in nasal mucosa, leads to hyperemia (increase in blood to nasal area when it wears off, stuffy again & need more)
- Mydriasis: stimulate alpha 1 receptor on the radial muscle, open up the pupil. There is a potential to get into the systematic and increase BP. Not used even though you can adjust for near and far vision.
- Used with local anesthetic to reduce spread of local anesthetic.

Front 88

What are examples of alpha agonists?

Back 88

- phenylephrine: mostly alpha 1 agonist but have some alpha 2 effect. effective ALL route (neosynephrine nasal spray as decongestant)
- Methoxamine: mostly alpha 1 agonist but have some alpha 2 effect - given via IV, IM

Front 89

What are beta agonists?

Back 89

• Selective beta 2 agonists (may have some beta 1 effects) used to treat asthma - active bronchodilator (orally/inhalation)
- side effects: potential to lower BP if gets in systemic and maybe tachycardia
- metaproternol
- terbutatine
- albuterol
- salmeterol

Front 90

What is prazosin?

Back 90

*alpha 1 antagonist (little alpha 2 effect)
- competitive reversible
- produce less tachycardia, used as a hypertensive (vasodilator)
- first dose side effect (orthostatic hypotension for the first 12 hr), given at night to avoid problems

Front 91

What are the characteristics of phenoxybenzamine?

Back 91

*non-competitive irreversible alpha 1 and alpha 2 antagonist
- relatively slow onset covalently binds to receptors, long durations 2-3 days
- get increase in circulating norepinephrine
• block vasoconstriction, vasodilate & decrease BP.
- increase in SNS tone, increase NE and Epi
• alpha 2 blockade blocks the negative feedback loop. giving increase in NE release
• phenoxybenzamine blocks reuptake into pre-synaptic receptors
- Increase NE, act on beta 1 because alpha 1 and 2 are blocke. Increase in HR (significant tachycardia)
• Epi increase mean pulse pressure, Norepi increase BP, give PBZ, Epi would decrease BP because all the alpha 2 receptors are block can only affect beta 2 receptors, so vasodilation & decrease BP
- If give Norepi goes back up because of smooth muscle contraction
- Side effects: tachycardia, serious orthostatic hypotension
- Used for people who have Raynaud’s syndrome extreme, vasodilator, pheochromocytoma (benign tumor usually associated w/ adrenal medulla, alpha and beta blocker)

Front 92

How does propanolol work?

Back 92

* non-selective beta 1 and beta 2 antagonist (olol= beta blocker) with mild/low level of local anesthetic activity
-Cardiovascular effects
• decrease in HR (normal individual)
• slight if at all decrease in BP in normal individual
• Hypertension (related to increase SNS or exercise) much greater decrease in HR and BP because of increase SNS tone, decrease in exercise tolerance by putting a ceiling to how fast HR is
- CNS effect
• Mild anti-anxiety effect, performance anxiety
• Decrease cognitive functions as well as HR
- Therapeutic Uses: Antihypertensive (use by itself or in combo w/ vasodilator to prevent tachycardia) Anti-Angina, Anti-dysrhythmic (prevent tachycardia by decreasing HR, rate of conduction and automaticity – cells of heart to generate their own action potential), Thyrotoxicosis (excessive thyroid hormone secretion which increase beta 1 receptors, block these receptors to prevent problems)
• Beta 1 blockade, decrease cardiac output (depends on hypertension that the person has to determine how much decrease there is)
• Decrease in norepi release/decrease in SNS tone due to CNS mechanism
• Decrease renin secretion (renin released by JG apparatus in kidney which has beta 1 receptors which is stimulated by circulating catechoamines
-decrease angiotensin system (decrease vasoconstriction)

Front 93

What are some precautions for beta blockers?

Back 93

1. Decrease cardiac function- don’t give to someone with cardiac failure
2. Withdrawal from chronic therapy can lead to hypertensive crisis- beta 1 receptors blocked- upregulation of beta 1 receptors- supersensitive (after 12 hr HR goes up a lot due to norepi and epi), DON’T MISS DOSES: need to taper off doses over 4-5 days to prevent hypertensive effect
3. Contraindicated in asthma because it has both beta 1 and beta 2 antagonist, will block bronchodilation by blocking beta 2 receptors- trigger asthma attack
4. caution in insulin-dependent diabetics (hypoglycemia is more common type of diabetes) Insulin decrease glucose- increase in epinephrine stimulates beta 2 receptors in liver to increase glycogenlysis/gluconeogenesis- increase glucose to overcome the decrease glucose, block beta = more severe hypoglycemia

Front 94

What are some selective beta-1 antagonists?

Back 94

- atenolol
- metaprolol
*safer for use in asthmatics and diabetics

Front 95

How do general anesthetics exert their effects?

Back 95

- by altering the nerve conduction properties of ligand-gated ion channels.
- They do this by potentiation of inhibitory (GABA-A and to a lesser extent glycine channels) ion channels or by blocking excitatory (NMDA-glutamate and nicotinic ACh) ion channels.
- Ligand-gated ion channels are Ionotropic – Fast Acting.

Front 96

How is GABA derived from glutamate?

Back 96

Glutamic acid decarboxylase removes COOH from glu forming GABA

Front 97

What are the 2 ligand-gated type receptors?

Back 97

*GABA-A receptor – brain
*Glycine – spinal chord and brainstem

Front 98

What are the volitile (inhaled) anesthetic prototypes?

Back 98

(Sevoflurane) (Also Nitrous oxide, halothane, enflurane, methoxyflurane, isoflurane, and desflurane)

Front 99

What are the intravenous anesthetic prototypes?

Back 99

(Etomidate) (Also Propofol, thiopental, midazolam, ketamine)

Front 100

Why is bethanechol only given orally?

Back 100

If give bethanechol via IV → major drop of BP (hypotension) b/c there are muscarinic receptors in vessels → stimulated relaxes → dilation (almost never stimulated since they are not innervated plus there is normally no circulating ACh, except when given in large dose as drug)