Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/100

Click to flip

100 Cards in this Set

  • Front
  • Back
What is chemical antagonism?
- chemical interaction between two drug molecules
- ex. chelation acid/base interaction, use of antacid which neutralizes drug.
What is physical antagonism?
- Physiological antagonism - two drugs that produce opposite effects through separate receptors
- NE - B1 → ↑ heart rate
- AcH - Muscarinic → ↓ heart rate
What is pharmacological antagonism?
Interaction at same receptor. Competitive & noncompetitive antagonism?
What is competitive antagonism?
- two drugs that act at the same site
- both act reversibly
- antagonist effects can be overcome by ↑ dose of agonist
What is noncompetitive antagonism?
- 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
What is potency?
• biological activity of drug per unit weight
• efficacy doesn’t tell much about potency
• not a useful term from pharmacological standpoint
What is a partial agonist?
• agonist that CANNOT produce a max response
• reduced efficacy compared to full agonist; does not deal with affinity
What kinds of drugs are receptors NOT involved?
• 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)
What are the 2 types of drug effects?
• 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
What is synergism?
Response of drugs A + B is greater than the algebraic sum.
What is potentiation?
The addition of drug B to drug A makes A more potent (a smaller dose of A required to generate response).
What is antagonism?
The response of drugs A + B is less than the algebraic sum.
What is the measure of theraputic index?
LD50/ED50 Larger theraputic index = worse
What is the measure of certain safety factor?
LD1/ED99
What are pharmacogenetics?
- 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
What is the placebo effect?
There can be a measured effect: when the person takes a drug, there is a release of enkephalins or psychological effects towards improvement.
What are the characteristics of the somatic nervous system?
- 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.
What are some characteristics of the autonomic nervous system?
- 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
What are the characteristics of the PNS?
- 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)
What are the characteristics of the CNS?
- 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
What are the effects of dual innervation on the heart?
- SNS works on B1 receptors to increase HR
- PNS works on muscarinic receptros to decrease HR
What are the effects of dual innervation on the GI tract?
- SNS decreases GI motility, B2 receptors relax, A receptors contract.
- PNS increases GI motility, increase contractions, muscarinic receptors relax sphincters
What are the effects of dual innervation in the iris?
- CNS contracts radial muscles, causing mydriasis
- PNS acts on circular muscles, causing miosis.
How do the effects of dual innervation present in the body?
- Normal innervated heart rate = 70 bpm
- denervated heart rate = 100-120 bpm
- dominant tone PNS
- PNS dominates except on blood vessels & sweat glands
What do botulinum toxin and black widow toxin do in the body?
- Botulinum toxin: blocks exocytosis process of acetylcholine on cholinergic synapse.
- Black widow spider toxin: increases exocytosis of acetylcholine on cholinergic synapses.
What is acetylcholinesterase?
Terminates action of ACh, primarily located in nerve terminals (cholinergic nerve terminals). (Target for anticholinesterase)
What is butyro cholinesterase?
aka "serum cholinesterase" "pseudo cholinesterase," no butyro choline in the body.
What is serum cholinesterase?
In liver, kidney, blood. Prevents you from having circulating acetyl cholinesterase.
What are the types of muscarinic receptors?
- 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.
What are parasympathomimetic drugs?
Drugs that have affinity and efficacy on muscarinic receptors.
What are the functions of parasympathomimetic drugs?
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
What happens at the cholinergic synapse?
• 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)
What are the properties of bethanechol?
* 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)
Why isn't acetylcholine used as drug therapy?
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
What is pilocarpine used for?
Used in glaucoma to reduce pressure, induce miosis.
What are cholinesterase inhibitors?
- indirect-acting (don’t act directly on the receptor)
- do NOT have affinity or efficacy for cholinergic receptors
- 2 classes: reversible vs. irreversible
What is physostigmine?
* 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)
What is neostigmine?
* 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
What are irreversible types of cholinesterase inhibitors used for?
toxicologic interest, mainly used as pesticides (very toxic) and nerve gases
What are some treatments for exposure to neostigmine?
○ Atropine
○ Artificial respiration (may have to be for days).
○ Pralidoxine (2-PAM)
What are organophosphates (w/ F-phosphorous group)?
- 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
What is DFP?
*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
What is malathione?
*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
What are the functions of parasympathomimetic drugs?
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
What happens at the cholinergic synapse?
• 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)
What are the properties of bethanechol?
* 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.
Why isn't acetylcholine used as drug therapy?
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
What are muscarinic antagonists?
• 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
What is atropine?
*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
What is scopalamine?
- 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
What are the quaternary amine muscarinic antagonists?
• 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
What are the muscarinic antagonists used to induce mydriasis?
- 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
What are the functons of ganglionic stimulants?
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
What do ganglionic blockades do?
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.
What is Mecamylamine?
* 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
Where does nicotine work?
Works on both NN & NM receptors, is a ganglionic stimulant & ganglionic blockade
What are competitive antagonists of somatic receptors on the NMJ?
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
What is the depolarizing agent on somatic receptors on the NMJ?
- 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.
What are the characteristics of the competitive antagonists of somatic receptors on the NMJ?
- 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
What are the characteristics of the depolarizing agents of somatic receptors on the NMJ?
- 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
How is tyrosine transported in the presynaptic node?
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
Where can PNMT convert norepi to epi?
In the adrenal medulla.
What are some mechanisms of norepi?
- 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
What is the key to getting rid of norepi?
- Reuptake (90% of norepi)
What are catecholamines metabolized by?
• catecholamine metabolized by monoamine oxidases (MAO) and catechole-O-methyl transferase (COMT)
What is MAO-A?
- 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
What is MAO-B?
- MAO-B, dopamine is preferred substrates (epi)
• Only form in the platelets
• MAO-B inhibitor used for Parkinson’s disease
- in brain/liver
What is COMT?
- 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
What are the actions of norepi?
• 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
What are the functions of epi?
- 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
What are the characteristics of alpha-1 receptors?
- 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)
What are the characteristics of alpha-2 receptors?
- Primarily pre-synaptic
- Inhibit release of norepi, epi and dopamine
(Also ACh)
- Inhibit insulin by stimulating pancreatic beta cells
- Cause platelet aggregation
What are the characteristics of beta-1 receptors?
- 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
What are the characteristics of beta-2 receptors?
- 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
What are characteristics of DA (dopamine) receptors?
- D1 (renal vasculature)
- vasodilate renal blood vessels (tx of shock)
What do beta 3 receptors do?
Increase lipolysis
What is isoproterenol?
*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
What is dobutamine?
*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
What is dopamine used for?
*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
How is tyramine an indirect-acting sympathomimetic?
- 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
What are the effects of amphetamine?
*indirect-acting sympathomimetic
- works on CNS (central) and PNS (peripheral)
What are the effects of ephedrine?
*indirect-acting sympathomimetic
- releases norepi and some direct beta 2 agonist effect
What are the effects of pseudoephedrine?
*indirect-acting sympathomimetic
- just a releaser, no direct beta 2 effect
What is reserpine?
*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)
How does cocaine act as an indirect-acting sympathomimetic?
- 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
What is Tranylcypromine?
- 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
What do alpha agonists do?
- 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.
What are examples of alpha agonists?
- 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
What are beta agonists?
• 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
What is prazosin?
*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
What are the characteristics of phenoxybenzamine?
*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)
How does propanolol work?
* 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)
What are some precautions for beta blockers?
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
What are some selective beta-1 antagonists?
- atenolol
- metaprolol
*safer for use in asthmatics and diabetics
How do general anesthetics exert their effects?
- 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.
How is GABA derived from glutamate?
Glutamic acid decarboxylase removes COOH from glu forming GABA
What are the 2 ligand-gated type receptors?
*GABA-A receptor – brain
*Glycine – spinal chord and brainstem
What are the volitile (inhaled) anesthetic prototypes?
(Sevoflurane) (Also Nitrous oxide, halothane, enflurane, methoxyflurane, isoflurane, and desflurane)
What are the intravenous anesthetic prototypes?
(Etomidate) (Also Propofol, thiopental, midazolam, ketamine)
Why is bethanechol only given orally?
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)