W3 : Flashcards
what are the effects of stimulation of å1 adrenoceptor?
the site is at blood vessels ; can be used for shock
agonist does the following :
- increase peripheral resistance
- increase BP
- mydriasis
- increase closure of internal sphincter of bladder
what are the effects of stimulation of ß1 adrenoceptor?
agonist does the following :
- tachycardia
- increase lipolysis
- increased myocardial contractility
- increase release of renin
can be used for HT failure
what are the effects of stimulation of ß2 adrenoceptor?
agonist does the following :
- vasodilation
- slightly decrease peripheral resistance
- bronchodilation
- increase muscle and liver glycogenolysis
- increase release of glucagon
- relax uterine smooth muscle (can prevent preterm delivery)
what are DIRECT acting adrenergic agonist?
these drugs act directly on å or ß receptors, producing effects similar to those that occur following stimulation of sympathetic nerves or release the hormone epinephrine from the adrenal medulla
there are two types of DIRECT acting adrenergic agonist :
- catecholemines
- noncatecholemines
epinephrine
direct acting adrenergic agonist
catecholemines
å1, å2, ß1, ß2
used in intense asthma
anaphylactic shock, etc.
dobutamine
direct acting adrenergic agonist
catecholemines
ß1
drug of choice to stimulate heart
dopamine
direct acting adrenergic agonist
catecholemines
å1, ß1
used to treat shock
phenylephrine
direct acting adrenergic agonist
noncatecholemines
å1
causes intense vasoconstriction
terbutaline
direct acting adrenergic agonist
noncatecholemines
ß2
used as bronchodilator (asthma)
albuterol
direct acting adrenergic agonist
noncatecholemines
ß2
used as bronchodilator (asthma)
salmeterol
direct acting adrenergic agonist
noncatecholemines
ß2
long acting bronchodilator
what are INDIRECT acting adrenergic agonist?
they cause norepinephrine release from presynaptic terminals or inhibit the uptake of nor-epinephrine
amphetamine
INDIRECT acting adrenergic agonist
has CNS stimulatory effects
used for narcolepsy, ADHD, appetite control
methylphenidate
same as amphetamine
INDIRECT acting adrenergic agonist
has CNS stimulatory effects
used for narcolepsy, ADHD, appetite control
what happens if a patient taking MAO-inhibitors eat lots of cheese?
- tyraminine is oxidized by MAO (manoamine oxidase)
- if patient taking MAP-inhibitors eat cheese, tyramine of cheese cannot be oxidized
- tyramine enters nerve terminal, and displaces store norepinephrine, thereby causing hypertensive crisis
[patient can carry 25mg tablets of chlorpromazine for emergency]
what are adrenergic antagonist?
these drugs bind to the adrenergic receptors and PREVENT their activation by endogenous epinephrine and norepinephrine
there are :
- å-adrenergic blocking agents (non-selective & selective)
- ß-adrenergic blocking agents (non-selective & selective)
- å & ß blockers
what are 2 families of adrenergic receptors?
and how are they further subdivided?
å adrenoceptor & ß adrenoceptor
å adrenoceptor are subdivided into two groups :
å 1 and å 2 - these are further subdivided into :
å 1A, å 1B, å 1C, å 1D & å 2A, å 2B, å 2C
MOA of non-selective å blocker (å1 and å2 blockers)?
there drugs block both å adrenergic receptors causing vasodilation and lowering blood pressure
Phenoxybenzamine
adrenergic antagonist(å1 and å2 blockers)
cause vasodilation and lower blood pressure
tx of pheochromocytoma (tumor of adrenal medulla, which produces too much epinephrine),
tx of hypertensive episodes
doxazosin
adrenergic antagonist
selective å1 blocker
tx. hypertension (can cause orthostatic hypotension
tamsulosin
adrenergic antagonist
selective å1A blocker
relaxes smooth muscle in urinary bladder neck and prostate–> improving urine flow in benign prostate hyperplasia
clonidine
adrenergic antagonist
å2 agonist (in blood vessel)
inhibits both sympathetic output from the brain and release of norepinephrine from nerve terminals–> reduce blood pressure
tx. hypertension
MOA ofß-adrenergic blocking agents?
all the clinically available ß-blockers are competitive antagonist
non-selective ß-blockers act at both ß1 and ß2 receptors, whereas cardioselective ß-antagonists primarily block ß2 receptors
propranolol
ß-adrenergic blocking agent (all tx Hypertension)
- tx. angima, cardia arrhythmias, myocardial infarction, congestive heart failure, hyperthyroidism, and glaucoma as well as serving in the prophylaxis of migraine HA
ci. ASTHMA
sotalol
ß-adrenergic blocking agent (all tx Hypertension)
- used for ventricular arrhythmias and tachycardia
ci. ASTHMA
metoprolol
ß1 - selective blocker
tx. hypertension, myocardial infarction, agina pectoris
atenolol
ß1 - selective blocker
which drugs are mixed å and ß blockers?
and their actions?
labetalol - å1, ß1, ß2 blockers (used for pre-eclampsia)
carvedilol - å1, ß1, ß2 blockers
ax. decrease BP wo reflec tachycardia
tx. hypertension
what are cautions needed to take when a patient w type 1 diabetes is to be given Propranolol, and why?
ß blocker leads to decreased glycogenolysis and decreased glucagon secretion.
Thus, very careful monitoring of blood glucose is essential bc pronounced hypoglycemia may occur after insulin injection. also reflex increase in HT rate that occurs in response to hypoglycemia is also blocked by ß-blockers
what are risks of withdrawing ß blockers? how can this be avoided?
tx w ß blockers when stopped abruptly risks severe precipitating cardiac arrhythmias.
the ß blockers must be tapered off gradually for at least a few weeks. Long term tx w ß antagonist leads to up-regulation of the ß receptors.
on suspension of therapy, the increased receptors can worsen angina or hypertension.
name excitatory and inhibitory neurotransmitters of brain?
excitatory neurotransmitters of CNS : acetylcholine, norepinephrine, dopamine, serotonin
inhibitory neurotransmitters of CNS : GABA, glycine
what are 3 types of anti-Parkinson drugs?
- dopamine replacement therapy
- dopamine receptor agonist therapy - AD agonists can be sued be although dopamine-releasing neurons have disappeared, the postsynaptic dopamine receptors are still present and functional. Administration of dopamine agonists to stimulate these receptors should therefore restore balance of inhibition and excitation in basal ganglia
- anticholinergic therapy - muscarinic antagonists used in Parkinson’s disease. they reduce Ach:Dopamine imbalance in striatum. side effects of these drugs include dry mouth, constipation, urinary retention, confusion.
what is etiology of Parkinson’s disease?
loss of dopamine-containing neurons that project from substantial nigra to striatum where they inhibit cholinergic (AcH) neurons.
Normally, striatum is connected to the substantial nigra by neurons that secrete the inhibitory transmitter GABA at their termini in substantia nigra.
In turn, substantial nigra sends neurons back to the striatum, secreting transmitter dopamine at their termini. This mutual inhibitory pathway normally maintains a balance. Destruction of cells of substantial nigra results in overproduction of Acetylcholine which triggers a chain of abnormal signaling, resulting in loss of control of muscle movement.
levodopa
- dopamine replacement therapy
metabolic precursor of dopamine
decarboxylated to dopamine in brain. DA does not cross blood-brain barrier
carbidopa
- dopamine replacement therapy
diminishes decarboxylation of levodopa (L-dopa) in peripheral tissues thereby prevent sits peripheral biotransformation
sinemet
- dopamine replacement therapy
combination of levodopa and carbidopa
selegiline
- dopamine replacement therapy aka deprenyl
inhibitor of monoamine oxidase_B (MOA-B), the enzyme that metabolizes dopamine in CNA
amantidine
- dopamine replacement therapy
antiviral drug effective in tx of influenza
also, enhances synthesis, release or reputed of dopamine from surviving neurons
what two drugs are used in dopamine receptor agonist therapy?
ropinirole & bromocriptione (powerful dopamine-receptor agonist)
etiology of Alzheimer Disease (AD)?
- formation of Beta-amyloid plaque
- neurofibruatory tangles
decrease in choline acetyltransferase (that catalyzes the transfer of acetyl group of acetyl CoA to choline, forming acetylcholine) and other markers of cholinergic neuron activity.
Eventually, cholinergic neurons die or are destroyed.
tx. focused on increasing amount of acetylcholine in synapse by inhibiting the breakdown of acetylcholine.
the most recent drug is an antagonist of N-methyl_Dasparate (NMDA) receptor (Glutamate receptor). Overstimulation of these receptors may be a mechanism of neurodegenrative process in AD.
donezepil
anti-alzheimer drug
cholinesterase inhibitor
memantine
anti-alzhiemer drug
NMDA antagonist
*antagonist of N-methyl-D-asparate (NMDA) receptor (Glutamate receptor). Overstimulation of these receptors may be a mechanism of neurodegenerative process in AD
appears to slow the progression of AD (slows the rate of memory loss)
what are Anxiolytic and Hypnotic drugs?
what are the 3 types?
tx. anxiety, epilepsy, sleep induction, and anesthesia, etc.
often called sedative-hypnotics or just anxiolytics.
cross tolerance occurs btw all the CNS sedative including the barbiturates, benzodiazepines (BZDs), and ethanol
- barbiturates
- benzodiazepines
- other
MOA of Barbiturates?
enhance the fx of y-aminobutyric acid (GABA) in CNS by enhancing the duration of chloride channel openings. this ax. hyper-polarizes the cell, and causes an increase in inhibition of CNS.
- produces sedation at low doses ; at high doses, can cause hypnosis, coma, death
- induce LV P-450 yste, so metabolism of other drugs will be altered in its presence
- physical deepness occurs after chronic use
*selection of particular barbiturate depends on duration of ax of agent, which in turn depends on its lipid solubility
what are withdrawal sx of barbiturates?
anxiety, nausea, vomiting, hypotension, seizures and psychosis
CV collapse may develop leading to death
phenobarbital
anxiolytic and hypnotic drug
long acting barbiturate (1-2 days)
used as anticonvulsant in epilepsy
amobarbital
anxiolytic and hypnotic drug
short acting barbiturate (3-8 hours)
used in anesthesia
MOA & ax of benzodiazepines
difference btwn barbiturates and benzodiazepines?
used most widely as anxiolytic drug
MOA : bind to specific site on Nueronal GABA receptors. this binding enhances the affinity of GABA receptors for GABA, resulting in more frequent opening of chloride channels. the increase chloride cases increased inhibition.
ax. : all BZD reduce anxiety and cause sedation
difference : unlike barbiturates, BZD reduce anxiety at does that do not produce sedation. some agents are used as anti-epileptic agents and some are used in induction of anesthesia. duration of ax and pharmacokinetic properties are important considerations in selecting drugs to be used.
dependence and withdrawal sx of benzodiazepines?
physical and psychological dependence of BZD can occur.
withdrawal : confusion, anxiety, agitation, restlessness
BZD with short half-life induce more abrupt and severe withdrawal reactions than do drugs w longer half-lives
diazepam (valium)
anxiolytic and hypnotic drug
long acting benzodiazepines
used for anxiety disorders, skeletal muscle spasm, spasticity from degenerative disorders such as MS and cerebral palsy
alprazolam
anxiolytic and hypnotic drug
long acting benzodiazepines
used as antidepressant, anxiolytic
tx of panic attacks
oxazepam
anxiolytic and hypnotic drug
long acting anxiolytic and hypnotic drug
useful for tx elderly patients and patients w liver dysfunction bc it does not rely on LV for metabolism
which benzodiazepines are used in tx of status epileptics and alcoholic withdrawal?
tx of stars epileptics : diazepam and lorazepam
alcoholic withdrawal : chlordiazepoxide
what are the advantages of using ZOLPIDEM?
what effect of this drug has been seen on vegetative state of patient?
anxiolytic drug
used for short term tx of insomnia, show no tolerance or withdrawal effects.
it is said to WAKE persistent vegetative state with brain injuries
MOA and use of flumazenil?
anxiolytic and hypnotic drug
a competitive benzodiazepines receptro antagonist
can be used to reverse the sedative effects of benzodiazepines after anesthesia or after overdose with BZD
