Adrenergic Agents and Blockers Flashcards by The Amazing Penisman

Adrenergic Agents are drugs that mimic actions of ________ and ________ and activate the _______ nervous system.

Epinephrine & Norepinephrine; sympathetic

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Adrenoreceptor that increases the heart rate:

Beta-1

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Identify the correct analogy of Dobutamine isomers:
Vasodilation: Vasconstriction

a. - isomer: + isomer
b. + isomer: - isomer

[Organ System Effects and Clinical Application of Sympathomimetics - Cardiovascular System -]

+ isomer: VASODILATION
- isomer: VASOCONSTRICTION

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Catecholamines are derived from these amino acids:

PHENYLALANINE & TYROSINE.

Phenylalanine -> hydroxylation by the enzyme phenylalanine hydroxylase -> Tyrosine -> L-DOPA -> DOPAMINE* -> NOREPINEPHRINE* (depending on cell type) -> EPINEPHRINE*

Catecholamines

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Changes During The Flight or Fight Response of the Sympathetic Nervous System (identify if inc or dec)

BRONCHODILATION

inc

Basta imagine mo lang ano mga changes saýo pag crunch time na for exams!
Beta-2 Adrenoreceptor activation.

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Changes During The Flight or Fight Response of the Sympathetic Nervous System (identify if inc or dec)

Saliva amount

dec

Nagddry ang mouth pag kulba or stress

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Changes During The Flight or Fight Response of the Sympathetic Nervous System (identify if inc or dec)

Sphincter Muscle Tone

inc

Better urinary retention pag fight or flight response!
* Mag-iincrease lahat ng sphincter tone

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Changes During The Flight or Fight Response of the Sympathetic Nervous System (identify if inc or dec)

Detrusor muscle tone

dec

Kasi pag nagcontract ang detrusor muscle ng bladder, mapapaihi ka. Better urinary retention ang nangyayari pag Fight or Flight response so dapat decreased detrusor muscle tone

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Changes During The Flight or Fight Response of the Sympathetic Nervous System (identify if inc or dec)

Blood Pressure

inc

Higher blood pressure kasi mas malakas pumping ng heart for increased circulation. Basta fight or flight response, isipin mo lahat ng changes na pwedeng mgcontribute to better performance + usual manifestation of stress + energy release.

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Manifestation of ULTIMATE EFFECTS during Fight or Flight response involves release of Norepinephrine from: ________ and Epinephrine is from _________

a Nerve terminals

b Adrenal Medulla

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Preganglionic axons synapse on neurons close to the:

SPINAL CORD

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A drug that inhibits the enzyme tyrosine hydroxylase and, therefore, catecholamine synthesis, which, as a consequence, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body.

[Happens at postganglionic nerve ending

METYROSINE

Order of inhibition at postganglionic nerve ending (palabas ng nerve ending):

METYROSINE (Inhibits tyrosine -> dopamine)
RESERPINE (Inhibits dopamine -> norepinephrine)
GUANITHIDINE (inhibit the Ca2+-dependent release of norepinephrine -> impedes propagation of impulses to nerve terminals)

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Adrenergic receptor that predominates in the presynaptic membrane.

Alpha-2

Location: Presynaptic adrenergic nerve terminals, platelets, lipocytes, SMOOTH MUSCLE, lower brainstem region (medulla oblongata).

Mechanism of Action: Gi, causes inhibition of adenyl cyclase, decreased cAMP (causes reverse effect of adrenergic activation) -> Therefore, Alpha-2 receptors behave like BLOCKERS!!

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DIRECT or INDIRECT

Adrenergic agonists that bind directly to receptors

[Classification of Adrenergic Receptors]

DIRECT

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DIRECT or INDIRECT

affects synthesis, storage, and release

[Classification of Adrenergic Receptors]

INDIRECT

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The mechanism of action of this adrenergic receptor involves G-protein type Gq.

(GPCR)

Gq-> activates Phospholipase C -> formation of IP3 and DAG -> increased intracellular calcium -> metabotropic

Alpha-1

Location: Postsynaptic effector cells, heart, SMOOTH MUSCLES (e.g. BLOOD VESSELS esp arteries), GLANDS

Basta pag Alpha receptors = Smooth Muscles.
Para Alpha Male, ikaw pinaka-SMOOTH
Remember na PRESYNAPTIC = Alpha-2, POSTSYNAPTIC = Alpha-1 (pero hindi lang siya ang postsynaptic adrenergic receptor)

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The most clinically significant adrenergic receptor in constriction and dilatation of blood vessels.

Alpha-1

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The mechanism of action of this adrenergic involves receptor Gs protein.

Gs -> stimulation of adenyl cyclase (effector) -> increased cAMP

All Beta Adrenergic Receptors

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Location of this adrenergic receptor is in Postsynaptic effector cells, especially HEART, LIPOCYTES, brain, presynaptic adrenergic and cholinergic nerve terminals, JUXTAGLOMERULAR CELLS of kidney.

Beta-1 Adrenergic Receptor:

Pag Beta-1 -> HEART

at JUXTAGLOMERULAR CELLS sa Kidney

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Location of this adrenergic receptor is mainly in Postsynaptic effector cells especially LIPOCYTES.

Beta-3

*Para ma-remember, murag bilbilon ang 3, so Beta-3 = LIPOCYTES

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Location of this adrenergic recepter is in Postsynaptic effector cells, especially SMOOTH MUSCLE (e.g. GI, blood vessels, lungs) and CARDIAC MUSCLE

Beta-2

*Para ma-remember, 2= 2 LUNGS. Beta-receptor na pinakarelated sa smooth muscle.

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This adrenergic receptor has an opposing effect to the Alpha-1 Adrenergic Receptor

Beta-2

Alpha-1 = More VASOCONSTRICTION
Beta-2 = More VASODILATION (also related to Bronchodilation)

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Most important Dopamine Receptors

D1 and D2

Found in: CNS, Brain, splanchnic and renal vasculature

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Dopamine Receptors that increase cAMP (Gs)

D1 & D5 (D1-like)

“1 is like an i, I for increase!”

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Most important adrenergic receptor found in SMOOTH MUSCLES (stimulation will increase cAMP)

Dopamine Receptor found in nerve endings

Subtypes of these adrenergic receptors have the most importance for understanding efficacy and safety of novel antipsychotic drugs

Dopamine Receptors. Dopamine Receptors are also most prominent in vertebrate CNS! Kaya siya ang pinaka-makacontribute sa brain-related drugs

Adrenoreceptor classification is based on

structure-activity relationships Altering ligand -> change in activity

This constant serves as the “fingerprint” to identify receptors.

Kd. - equilibrium dissociation constant - the ratio of concentrations when equilibrium is reached in a reversible reaction (when the rate of the forward reaction equals the rate of the reverse reaction)

Decrease in Kd (equilibrium dissociation constant) would lead to Increase or Decrease in affinity of the ligand?

Increase. Lesser dissociation, more binding. ↓Kd = ↑ affinity

TRUE or FALSE. Drugs with different affinities can | have the same potencies in eliciting a clinical effect.

FALSE. Drugs have different affinities because they have different potencies in eliciting a clinical effect Notes on affinity regarding structure of catecholamines

Structure-activity relationships are the basis for adrenoreceptor classification. What are the important structural characteristics of the following catecholamines? Epinephrine Norepinephrine Isoproterenol

Epinephrine – with methyl group Norepinephrine - NO methyl group - "No"epinephrine Isoproterenol – isopropyl group

TRUE or FALSE. Only little amounts is needed for ISOPROTERENOL to achieve maximal effect as compared to NOREPINEPHRINE and EPINEPHRINE [EFFECTS OF ADRENERGIC RECEPTOR ACTIVATION > EFFECT ON FORCE OF CONTRACTION]

TRUE. ISO – more potent, same efficacy, much lower Kd than E ISO also has greatest affinity; E & NE – almost the same affinity Remember: The lower the Kd, the higher the affinity, the more potent it is.

Adrenergic agonists inhibit the degradation of:

cAMP. β and α are metabotropic receptors, meaning they increase cAMP

The most potent CATECHOLAMINE in BRONCHODILATION [EFFECTS OF ADRENERGIC RECEPTOR ACTIVATION > EFFECT ON BRONCHODILATION]

ISOPROTERENOL *Ang adrenergic receptor naman na nagccause ng bronchodilation ay Beta-2 ISO>E>=NE ang trend sa Effects on Contraction Adrenergic Receptor Activation. ISO>E>>NE naman sa Effects on Bronchodilation E >= NE >> ISO naman sa Effect on Vasoconstriction

The response of any cell or organ to a sympathomimetic depends on the ______ and ______ of adrenergic receptors. [CLASSIFICATION OF ACTIONS OF ADRENERGIC RECEPTORS]

DENSITY & PROPORTION

CLASSIFICATION OF ACTIONS OF ADRENERGIC RECEPTORS:

1. Peripheral excitatory action 2. Peripheral inhibitory action 3. Cardiac excitatory action 4. Metabolic action 5. Endocrine actions 6. Actions in the CNS 7. Prejunctional actions

Identify the Adrenergic Receptor! Dilates renal blood vessels (the receptor with most bearing)

Identify the Adrenergic Receptor! Modulates transmitter release

D2. It is found on nerve endings

Identify the Adrenergic Receptor! Inhibition of transmitter release

Alpha-2. Remember na presynaptic siya.

Identify the Adrenergic Receptor! Erects hair

Alpha-1. Pag smooth muscle contraction. Hair erection is due to contraction of Pilomotor smooth muscle.

Identify the Adrenergic Receptor! Increase Renin release

Beta-1. - Basta pag Beta-1, associated agad sa HEART CONTRACTION at JUXTAGLOMERULAR CELLS ng KIDNEYS (Hence, association with renin release.)

Identify the Adrenergic Receptor! Activates lipolysis

Beta-3 - Remember mo lang yung bilbil ng 3

Identify the Adrenergic Receptor! helps prevent premature labor

Beta-2 - pnemonic: It takes -2- to make B-aby.

Identify the Adrenergic Receptor! Inhibition of lipolysis

Alpha-2

Identify the Adrenergic Receptor! can improve urine output

D1. Remember yung effect niya na mag dilate ng renal blood vessels.

Identify the Adrenergic Receptor! Promotes potassium uptake in skeletal muscles

Beta-2 - Pag beta-2, mostly dilation effects, so less contraction, meaning less Na and more K

Identify the Adrenergic Receptor! stimulate phospholipase C

Alpha-1 The mechanism of action of this adrenergic receptor involves G-protein type Gq -> phospholipase C

What are the selective, direct-acting, adrenergic agonists?

α1 - Phenylephrine α2 - Clonidine β1 - Dobutamine β2 - Terbutaline

What are the non-selective, direct-acting, adrenergic agonists?

α1 α2 Oxymetazoline β1 β2 Isoproterenol α1 α2 β1 β2 Epinephrine α1 α2 β1 Norepinephrine

Adrenergic agonists which are Indirect-acting RELEASING AGENTS -

Amphetamine Tyramine - actions are dependent on the release of endogenous catecholamines; increases the release of NE from the vesicles (indirect)

Adrenergic agonists which are Indirect-acting UPTAKE INHIBITORS

Cocaine Tricyclic Antidepressants -> decreases re-uptake of NE (remains in the synapse, prolonging the action)

Indirect-acting Adrenergic Agonists that block the degradation of NE

MAO/COMT Inhibitors

What are the mixed-acting adrenergic agonists?

Ephedrine α1 α2 β1 β2 and releasing agent Dopamine D1 D2 α β and releasing agent can bind to all different kinds of receptors; both bind to the receptor and prevent reuptake of catecholamines

increased production of NE (but cannot be measured so request for urine vanilodilic acid)

PHEOCHROMOCYTOMA

TRUE or FALSE. Receptor Specificity/ Selectivity is absolute.

FALSE. Receptor Specificity/ Selectivity is RELATIVE, NOT ABSOLUTE! - It is dependent on the amount of drug available! For example, beta-1 agonist can bind with beta-2 receptor if it is given at a higher concentration than the beta-2 agonists. Beta-2 is simply more favored.

Dopamine Effects at different blood concentrations

0.3ug/mL -> D1 -> Diuresis 0.7ug/ml -> Beta-1 -> increased heart contractility 1 ug/ml -> Alpha receptors -> increased heart rate, arrythmia

Beta-1 receptor agonist effect on cardiovascular system

Positive chronotropic effect (increased pacemaker activity, increased heart rate) Positive inotropic effect (intrinsic contractility is increased)

Adrenergic blocker that inhibits VMAT (Vesicular Monoamine Transporter)

RESERPINE

Adrenergic blocker that Can inhibit the Ca2+-dependent release of norepinephrine

GUANITHIDINE

Symphatomimetic drug that causes myrdriasis but treats glaucoma

PHENYLEPHRINE

Drug used in the treatment of diarrhea in diabetics with autonomic neuropathy

CLONIDINE (Alpha-2 agonist)

an adrenergic agonist that is also a nasal decongestant

PHENYLEPHRINE

Beta-receptor agonist that helps relax uterine smooth muscle, used during preterm labor -

Ritodrine, Terbutaline

A mixed-acting drug that could cross BBB, has prolonged action like amphetamine, could be given orally

EPHEDRINE Basta Blood-brain barrier -> EPHEDRINE

Agonist that could cause congestive heart failure

DOBUTAMINE

Toxicity related to this drug could lead to restlessness, tremor, anxiety, paranoid state.

AMPHETAMINE

Toxicity related to this drug could lead to convulsions, hemorrhage, arrhythmias, MI

COCAINE

prodrug converted to alpha-methylnorepinephrine. Also an alpha-2 agonist

METHYLDOPA

Selective Alpha 1 Adrenergic Antagonists

PTD Prazosin, Terazosin, Doxazosin SIN is antagonistic to the alpha.

Use of this alpha antagonist leads to relaxation of both arterial and venous vascular smooth muscle as well as smooth muscle in prostate

PRAZOSIN PR-prostate - relaxation

Nonselective α1 antagonists

PHENTOLAMINE & PHENOXYBENZAMINE - PP

Beta-Blocker used for migraine

PROPRANOLOL

Beta-1 selective Adrenergic Antagonists used in patients with asthma/COPD, diabetes, peripheral vascular disease

METOPROLOL, ATENOLOL

Contraindications to Beta-Blockers

Remember na beta- receptor function ay mainly for vasodilation - Asthma, other bronchospastic condition - Severe bradycardia - AV block, bradycardia-tachycardia syndrome - Adverse Effects: o Related to consequences of β blockade; o Sedation, fatigue, depression (highly lipophilic drugs), impaired exercise tolerance, insomnia, exacerbation of peripheral vascular disease, erectile dysfunction

Beta-blocker with longest half-life: up to 24 hours, excreted unchanged

NADOLOL

Differences in metoprolol plasma clearance is dependent on the genotype of which CYP

CYP2D6