Test 1: Wk3: 3 Adrenergic Agonists and Antagonists - Salisbury Flashcards
indirect sympathomimetic agents MOA
indirect acting drugs ⬆️ The availability of NE or EPI
4 indirect acting releasing agents
- Amphetamine
2 Methylphenidate
3 Tyramine
4 Ephedrine
Ephedrine can also stimulate … and …
alpha and Beta Receptors
Indirect acting Releasing Agents uses
ADHD
Hypotension
2 Indirect Acting uptake inhibitors
1 cocaine
2 TCA impiramine
Indirect Acting uptake inhibitors uses
Depression
Indirect Acting MAO inhibitors
TranyIcypromine
Phenezine
selegiline
Indirect Acting uptake inhibitors COMT inhibitors
Intacapone
Talcapone
Indirect Acting uptake inhibitors MAO inhibitors uses
Depression
Avoid … w/ MOA inhibitors
Tyramine causes hypertensive crisis
Indirect Acting uptake inhibitors COMT inhibitors uses
Parkinson’s
⬆️ Levodopa
Direct Acting sympathomimetic Drugs
catecholamines
Noncatecholamines
catecholamines (5)
1 Dopamine 2 Isoproterenol 3 NE 4 EPI 5 Dobutamine DINED
Can catecholamines and noncatecholamines be given orally
No they’re too rapidly metabolized
Noncatecholamines (3)
1.phenylephrine
2 ephedrine
3 amphetamine
a 1
vasoconstriction
B2
vasodilation
Norepinephrine Receptors
a1 a2 B1»_space;> B2
Epinepherine Receptors
a1 a2 B1 B2
Isoproteronol Receptors
B1 B2»_space;> a1
Norepinephrine effect on pulse rate
Slight decrease a1»_space; B2
Epinephrine effect on pulse rate
Slight increase, dose Dependent B2 > a1
Isoproterenol effect on pulse rate
Increase B2»_space;> a1
NE effect on BP
increase
Epi effect on BP
slight increase
Isoproterenol effect on BP
slight decrease
NE effect on peripheral resistance
increase
Epi effect on peripheral resistance
slight decrease
Isoproterenol effect on peripheral resistance
decrease
Low dose Epi
higher affinity for B2
TPR decrease
Epi high dose
Epi receptor selectivity is lost
a1=B2
TPR increase and MBP
Epi reversal
Phenoxybenzamine
a1 and A2 block
adrenergic agonists MOA
mimic effects of SNS - sympathomimetic
adrenergic agonists exception
a2 receptor agonists are sympatholytic
Epinephrine is an agonist at
a1, a2, B1, B2
Epi causes
bronchodilation - B2
Epi CV effects low dose
vasodilation - B2 more sensitive than a receptors
tachycardia - direct B1
Epi CV effects low dose net
net effect ⬆ TPR, slight ⬆ BP ⬆HR
Epi CV effects high dose
vasoconstriction - a receptor activation dominates)
⬆ TPR ➡ ⬆ BP
direct B1 ➡ ⬆HR
Epi CV effects high dose net
⬆ TPR ⬆BP ⬆HR
Epi metabolic effects
- hyperglycemia
- ⬆ glycogenolysis and gluconeogenesis
- ⬆ blood glucose
- ⬆ free FAs in blood
- ⬇ plasma K+
Epi a2 does what to insulin secretion
⬇⬇
Epi B2 does what to insulin secretion
⬆
Epi a2>B2 net effect on insulin
⬆
Epi what receptor ⬆ glycogenolysis and gluconeogenesis
B2
Epi — receptors in adipocytes — FFAs in blood
B; ⬆
Epi — receptors — K+ plasma concentrations
B2; ⬇
they increase K+ uptake thus lowering it in plasma
Epi therapeutic uses (5)
1 Anaphylaxis 2 Bronchospasm 3 Cardiac Arrest 4 prolong action of local anesthetic 5 glaucoma
Epi kinetics
catecholamine
not effective orally must be IV
Epi adverse effects (4)
1 marked hyperglycemia
2 cardiac stimulation
3 vasoconstriction
4 CNS stimulation
Epi vasoconstriction adverse effects
hypertension, slough at injection site
Epi CNS Stimulation Adverse Effects
⬆ respiration, apprehension, tremor
Epi contraindications
tachyarrhythmias, hyperthyroidism
⬆ toxicity with MAO inhibitors
NE is an agonists at
a1, a2, B1
NE CV effects
vasoconstriction ➡ ⬆TPR ➡⬆ mean BP
+- HR ➡ direct B effect + reflexes ➡ +- HR
NE CV net effects
⬆ TPR ⬆ BP +- HR
NE therapeutic effects
septic and cardiogenic shock
MOA vasoconstriction + inotropic
NE Kinetics
catecholamine IV only
NE adverse effects
cardiac - arrhythmias, angina
vasoconstriction - hypertension
NE Contraindications
tachyarrhythmias, hyperthyroidism, hypertension
⬆ toxicity with MAO Inhibitors
⬆ toxicity with cocaine and reuptake inhibitors
Dopamine is a direct — at —- — receptors
agonist, dopaminergic, D1
what does dopamine do
dilates renal, splanchnic, cerebral, and coronary vessels
Causes release of NE
Dopamine CV Low dose
D1 receptor mediated selective vasodilation of renal and splanchnic vessels
Dopamine CV moderate dose
D1 receptor mediated vasodilation ➡ ⬇ TPR
Direct and reflex B1 receptor mediated effects ➡⬆HR, ⬆ CO
+- BP
Dopamine CV High dose
a1 receptor mediated vasoconstriction > D1 mediated vasodilation ➡ ⬆ TPR
B1 receptor Cardiac Effects ➡ ⬆ HR
⬆ BP
Dopamine protects the
kidney
Dopamine therapeutic effects
Shock
Acute CHF
Dopamine Shock tx MOA
renal vasodilation, peripheral vasoconstriction, +inotrope
Dopamine Acute CHF tx MOA
renal vasodialation, +inotrope
Dopamine Kinetics
catecholamine
Dopamine Adverse Effects
similar to NE
cardiac - arrhythmias, angina
vasoconstriction - hypertension
Pseudoephedrine has direct effects on
adrenergic receptors + release of NE
Pseudoephedrine effects
vasoconstriction +- HR
from NE
Pseudoephedrine therapeutic indications
Decongestant
vasoconstriction of nasal mucosa
Pseudoephedrine adverse effects
hypertension
insomnia
Dobutamine: effects
complex action of enantiomers on α 1 , ꞵ1 , ꞵ2 receptors
Dobutamine Effects in pts with CHF
+ inotrope → ↑ CO
±HR, ±TPR, ±BP
Dobutamine Therapeutic indications
acute CHF (MOA: + inotrope)
Dobutamine
catecholamine (t1/2 = mins, IV only)
Dobutamine Adverse effects
arrythmias, ↑ MVO2, ↑ AV nodal conduction
hypertension in some pts
Isoproterenol agonist at
ꞵ1 & ꞵ2 receptors
Isoproterenol Effects
bronchodilation
CV effects
Isoproterenol CV effects
direct ꞵ2 effects → vasodilation (in sk musc ) → ↓TPR, ↓ BP
direct ꞵ1 + reflex ( ꞵ1) cardiac effects → ↑ HR
Isoproterenol Net cardiac effects
net effect → ↓ TPR, ↓ BP, ↑ HR
Isoproterenol Therapeutic effects
Reverse Bronchospasm ( β 2 effect)
cardiac arrest (MOA: + chronotrope , +
heart block (MOA: reduces block by ↑ AV
how does Isoproterenol reverse bronchospasm
β 2 effect
how does Isoproterenol help cardiac arrest
MOA: + chronotrope , +inotrope
how does Isoproterenol help heart block
reduce block by ⬆ AV Conduction
Isoproterenol Kinetics
catecholamine (not effectively orally, t1/2 = mins)
Isoproterenol Adverse effects
cardiac stimulation
tremor
Isoproterenol Contraindications/precautions
tachyarrhythmia
hyperthyroidism
3 Selective
α 1 receptor agonists
Phenylephrine, Methoxamine, Midodrine
Phenylephrine, Methoxamine, Midodrine Effects
mydriasis
vasoconstriction → ↑ TPR → ↑ BP
reflex ↓ HR
Phenylephrine, Methoxamine, Midodrine Therapeutic uses
mydriatic
decongestant
prolonged action of local anesthetics
hypotension
Phenylephrine, Methoxamine, Midodrine
Adverse effects
hypertension
reflex bradycardia
Selective
α 2 receptor agonists
Clonidine
Clonidine Effects
CNS → ↓sympathetic outflow → vasodilation → ↓ TPR → ↓ BP
little reflex ↑ HR (CNS effect → ↑ vagal tone → ±HR despite ↓ BP
Clonidine is a
sympatholytic
a2 agonist
Clonidine Therapeutic uses
Hypertension
drug addiction
ADHD
how does Clonidine improve hypertension
⬇ sympathetic outflow from CNS
Clonidine Adverse effects
hypertensive crisis upon sudden withdrawal (rebound hypertension)
sedation
sexual dysfunction
Selective
β 2 agonists
β 2»_space; β 1
Albuterol
Albuterol Effects
bronchodilation
vasodilation → reflex ↑ HR
Albuterol Therapeutic uses
reverse bronchospasm
asthma, COPD
Albuterol Adverse effects
cardiac stimulation (arrhythmias, angina)
can activate β1 receptors at high doses
reflex tachycardia due to baroreceptor reflex
Tremor
Albuterol contraindications/precautions
tachyarrhythmia
hyperthyroidism
Selective
β 2 agonists Long acting
Salmeterol
Formoterol
Induce bronchodilation for up to 12 hours
Adrenergic Receptor Antagonists function
inhibit action of endogenous
NE & Epi at receptor sites
Also inhibit actions of exogenously administered drugs that function as adrenergic agonists
Nonselective
α 1 & α 2 antagonists
Phenoxybenzamine
Phenoxybenzamine
Phenoxybenzamine
non competitive block at α 1 & α 2 receptors
Phenoxybenzamine Effects
vasodilation → ↓ TPR → ↓ BP
reflex ↑ HR (also blocking α 2 ↑ sympathetic outflow from CNS to
induce tachycardia)
Phenoxybenzamine Kinetics
slow onset
long lasting
effective orally
Phenoxybenzamine Therapeutic uses
preoperative or chronic Tx of pheochromocytoma (with β blockers)
Tx of reversible vasospastic disease
Phenoxybenzamine Adverse effects/contraindications/precautions
tachycardia, arrhythmias, angina
orthostatic hypotension
sexual dysfunction
Phentolamine function
Competitively blocks α 1 & α 2 receptors
Phentolamine vs Phenoxybenzamine
faster onset/shorter duration of action (t1/2 = mins)
must be administered IV
Phentolamine Therapeutic uses
hypertensive crisis (e.g. clonidine withdrawal)
during surgical removal of pheochromocytoma
reversible vasospastic disease (e.g. frostbite)
Relatively selective α
1 Receptor
Antagonists
Doxazosin (Prazosin, Terazosine, Alfuzosin
Doxazosin (Prazosin, Terazosine, Alfuzosin) Effects
arterial dilation → ↓ TPR → ↓ BP
little to no reflex ↑ HR
relaxation of the bladder sphincter and urethra
Doxazosin (Prazosin, Terazosine, Alfuzosin) therapeutic uses
↑ urine flow in benign prostatic hypertrophy
hypertension
Doxazosin (Prazosin, Terazosine, Alfuzosin)
adverse effects
first dose syncope → due to ↓ BP
begin therapy at night
occurs in volume depleted patients
Tamsulosin function
selective inhibition of α 1A receptors may provide some selectivity for sphincter and urethra
Tamsulosin effects
relax bladder sphincter
Tamsulosin Therapeutic uses
↑ urine flow in benign prostate hypertrophy
Tamsulosin Adverse effects/contraindications/precautions
orthostatic hypotension
Yohimbine is a
(competitive antagonist that is selective for α 2 receptors)
Yohimbine function •
In the CNS
→ ↑release of NE → blood pressure and heart rate
Yohimbine effects
↑ motor activity and produces tremors.
β 1 Receptor inhibition
heart
↓ automaticity → ↓ HR
↓ contractility
↓ conduction velocity
β 2 Receptor inhibition
bronchonstriction
↓ glycogenolysis
↑ TPR
Nonselective β Receptor Antagonists
Propranolol
Propranolol MOA
competitive inhibition of β 1 = β 2
Propranolol CV effects heart
- ↓ automaticity → HR
- ↓ contractility → CO
- ↓ myocardial oxygen consumption
- ↓ AV nodal conduction velocity
Propranolol CV effects long term
↓ BP
↓ CO
↓ renin release
±TPR
Propranolol: non
CV Effects
Bronchoconstriction
↓ intraocular pressure in glaucoma (↓ aqueous humor
- ↓ lipolysis → ↓ FFA → ↑ triglycerides
- ↓ HDL
Propranolol Metabolic Effects
↓ glycogenolysis → prolong hypoglycemic event
↓ insulin release → hyperglycemia
Propranolol Kinetcs
orally effective (poor availability)
Hepatic metabolism
Propranolol Kinetcs
orally effective (poor availability)
Hepatic metabolism
Propranolol Therapeutic uses (9)
hypertension
chronic stable angina
arrhythmias
Post MI
hyperthyroidism
pheochromocytoma
migraine prophylaxis
stage fright
essential tremors
Propranolol Adverse Effects and Contraindications
slide 54
Timolol, Nadolol
Similar to propranolol (competitive inhibition of β 1 = β 2)
Timolol, Nadolol Therapeutic uses
similar to propranolol (hypertension, post MI)
timolol glaucoma (also levobunolol
Cardioselective
ꞵ1 Receptor
Antagonists
Metoprolol, Atenolol
Metoprolol, Atenolol function
inhibit ꞵ1 > ꞵ
Metoprolol, Atenolol are Preferred over non specific ꞵblockers in pts with:
diabetes (especially in patients that are prone to hypoglycemic reactions)
Raynaud’s syndrome
COPD (still contraindicated in asthmatics)
Metoprolol, Atenolol Kinetics
metoprolol hepatic metabolism
atenolol renal elimination
Metoprolol, Atenolol Therapeutic uses:
similar to propranolol
CHF metoprolol
Esmolol
Cardioselective
ꞵ1 Receptor
Antagonists
Esmolol function
very short acting Cardioselective ꞵ blocker
Esmolol kinetics
metabolized by red blood cell esterase
Esmolol Therapeutic uses
used as antiarrhythmic (IV only)
Mixed Action
ꞵ Blockers
Carvedilol, Labetalol
Carvedilol, Labetalol function
non specific ꞵ block + α 1 blocker effects
antioxidant activity
Carvedilol, Labetalol effects
non specific ꞵ block + α 1 blocker effects
↓ TPR
±HR, CO
↑ HDL
Carvedilol, Labetalol Therapeutic uses
hypertension
CHF
Carvedilol, Labetalol Adverse effects/contraindications/precautions
same as other β blockers
+ hypotension due to α1 block
Nebivolol function
Cardioselective β 1 block + NO mediated vasodilation
Nebivolol effects
↓ TPR
±HR, CO
Nebivolol Therapeutic uses
hypertension, CHF
Nebivolol Adverse effects/contraindications/precautions
same as other ꞵ blockers
+ more prominent hypotension due to NO mediated vasodilation