Week 3 Flashcards
Alpha 1 receptors
Adrenergic receptors
Norepinephrine and Epi binds to these receptors.
Activation leads to sympathetic response.
Fight or flight– need increased BP, to see more, don’t pee yourself, more more glucose
Vasoconstriction
Pupil dilation
Urinary retention and contraction
Glycogenolysis in liver- glucose production
Inhibition of renin release in kidney (regulation of BP)
Alpha 2 receptors
Adrenergic receptor
GI protein-coupled receptors
Located on presynaptic nerve endings, and when activated cause decrease in intracellular CAMP, which inhibits further release of norepi.
Also located on pancreatic outlets and lead to decreased insulin secretion.
Beta 1 receptors
Adrenergic receptor
Located on heart and when activated, lead to increase HR, contractility, and AV node conduction.
Also on kidneys, which lead to increased renin, which increases BP.
Beta 2 receptors
Adrenergic receptors Lung- bronchodilation Skeletal muscle-relaxation-vasodilation Smooth muscle in GI and uterus- decreased GI motility and inhibition of labor. Pancreas- increase in insulin secretion
Adrenergic agonists
Catecholamine and noncatecholamine. Differ in oral usability, duration of action, and CNS penetration.
3 types:
Direct acting agonists
Indirect acting agonists
Mixed-action agonists
Cells become desensitized if exposed for too long.
Direct acting adrenergic agonists NON-SELECTIVE
Non-selective (can act of alpha or beta)
Catecholamines (only by injection)
Binds to alpha or beta receptor and mimic effects of epinephrine, norepinephrine, and dopamine in our bodies.
Most common:
epinephrine
Acts on beta and alpha. Leads to vasoconstriction, increased cardiac output, bronchodilation (alpha)
Norepinephrine: mostly stimulates beta. Vasoconstriction and increase in BP
Dopamine: stimulates all 3 in dose-dependent manner. Low dose stimulates dopa receptors, higher doses stimulates B1, then A1
Indirect acting adrenergic agonists
Enhance effects of epi and norepinephrine by inhibiting their reuptake or degradation (by MAOs). Don’t work directly on postsynaptic receptors.
Cocaine and amphetamines
Stimulate alpha 1 and beta 1 which stimulates a sympathetic response. Increase in BP and HR
Mixed-action adrenergic agonists
Stimulation of adrenergic receptors by Direct binding and as well as release of stored norepinephrine from presynaptic terminals.
Ephedrine and pseudoephedrine. Noncatecholamines long-acting.
Alpha1 antagonists (blockers)
(-osin)
Adrenergic antagonist
Can be selective or non-selective
Reversible block effects of catecholamines at the post-synaptic alpha1 receptors in vascular smooth muscle and bladder neck and prostate.
(-osin) vascular smooth muscle. Decrease BP and vascular resistance. Relief of urinary difficulty in BPH. prazosin, doxazosin (good tx for HTN) tamsulosin (good for BPH), etc. can block receptors in different sites which is why some are better for HTN and some are better for BPH. Side effects or this tactic hypotension.
Alpha2 blockers- not used in humans
Doxazosin
Alpha1 selective antagonist (alpha1 blocker). Relaxes vascular smooth muscle, leading to decrease peripheral resistance and decreased BP.
Side effects: orthostatic hypotension, HA, and nasal congestion.
Beta blockers
Selective and non-selective. Also grouped into generations.
Competitive inhibitors of beta adrenergic receptors. Prevent catecholemines like epi and norepinephrine, as well as other beta agonists from binding.
Decrease HR, contractility of ventricles, AV conduction, decreases peripheral resistance, decreases BP (through decreases renin), increased bronchial constriction, decreased intraoccular pressure, and inhibition of lipolysis.
HTN, CHF, etc. also used in glaucoma and migraine prophylaxis.
Propranolol is the prototype
Onset of action: 1-2 hrs orally. Rapidly absorbed.
Half-life 3-6 hrs
Excreted in urine
Drug interactions: alcohol, nitrates, cold remedies, Clonidine
Don’t take within 8 hrs of another dose. Food enhances bioavailability
1st generation beta blockers (nonselective)
Block b1 and b2.
Propanolol, sotalol, basilisk, timolol.
Can also penetrate CNS which is why it is effective in migraine prophylaxis.
Mostly effective on B1, leading to decreased HR, contractility, and BP. however the effects on B2 cause bronchoconstriction, so not recommended for people with COPD or asthma
Beta1- dobutamine. Increased HR and COP, acute CHF.
2nd generation (beta-1 selective)
Cardioselective BB
more suitable for people with chronic respiratory conditions. However with increased doses, B1 selectivity can be lost.
Atenolol, esmolol, metoprolol, acebutolol, bispropolol.
3rd generation beta blockers
Both non selective and selective BB. also act on blood vessels to create vasodilation (alpha). Very effective in treating HTN. especially in CHF patients.
Non-selective: Carvedilol and labetolol. Peripheral vasodilation by blocking beta and alpha 1
B1 selective- nebivolol and betaxolol. Produce vasodilation.
Sympathetic (adrenergic) nervous system
Part of the autonomic nervous system. Sympathetic neurons come from thoracic and lumbar regions of the spinal cord.
Epinephrine and norepinephrine activate alpha, beta, and dopamine receptors, called adrenergic receptors
Fight or flight. Dilation of pupils, inhibition of saliva, relaxation of the airways, acceleration of the heart, inhibition of digestion, stimulation of glucose release in the liver, inhibition of intestinal activity, inhibition of gallbladder, stimulation of adrenal medulla (secretion of epi and norepinephrine), relaxation of bladder, and stimulation of ejaculation or vaginal contractions.
Parasympathetic (cholinergic) nervous system
Part of autonomic nervous system.
Releases ACh- counterbalances sympathetic activity.
Activates muscarinic receptors and nicotinic receptors (cholinergic receptors).
Rest and digest. Feed and breed.
Cholinergic neurons
Use acetylcholine to send messages in the nervous system
Two types of receptors: nicotine and muscurinic
Primarily found in the parasympathetic system. Also have role in sympathetic innervation of the sweat glands and blood vessels in skeletal muscle.
Acetylcholine binds to postsynaptic receptors, which leads to cholinergic response. Also binds to presynaptic receptors, inhibiting the release of more acetylcholine (negative feedback loop).
Adrenergic neurons
Use neurotransmitters epinephrine and norepinephrine to transmit messages in the nervous system. Also Dopamine.
Nicotinic receptors
Type of cholinergic receptor
When acetylcholine binds, allows Na+ to flow into the cell.
Muscurinic recepto
Type of cholinergic receptor
M1- digestive tract
M2- cardiac
M3- smooth muscle of eye, lungs, and sweat and lacrimal glands.
Direct acting cholinergic agonists
Mimic effects of acetylcholine by binding to muscarinic or nicotinic receptors.
Drug: acetylcholine. Nonspecific cholinergic effects and easily inactivated by cholinesterase. Limited clinical uses. When injected causes decrease COP, Hr, BP, and increased GI activity. Pupillary construction and decreased intraoccular pressure.
Indirect cholinergic agonists
Cholinesterase inhibitors
Binds to acetylcholinesterase enzyme. Leads to buildup of acetylcholine.
endrophonium. Used for diagnosis of MG. expect to see increase in muscle strength. Short-acting. Physostigmine- stimulates both receptors.
Physostigmine- can bind to both nicotinic and muscurinic. Used in tx of OD of anti cholinergic drugs such as atropine.
Neostigmine- effects of MG.
Donezipril (Aricept)
All reversible. Irreversible type is sarin gas.
Cholinergic adverse effects
DUMBELLS
Diarrhea Urination Miosis/ muscle weakness Bronchorrhea Bradycardia Messi's Lacrimation Salivation/sweating
Cholinergic antagonists
Anticholinergics
Parasympatholytics
1) anti muscarinic agents
2) ganglionic blockers
3) neuromuscular blockers
Atropine, Dicyclomine (Bentyle), trihexyphenidyl
Antimuscarinic drugs (AKA anti cholinergic)
Block muscarinic receptors and their functions.
Atropine is prototype
Scopolamine- Prevents motion sickness and post operative nausea.
Ipatroprium- Decreased contractility in lungs, leading to bronchodilation and decreases sputum production.
Treatment in overactive bladder (oxybutinin)
Parkinson’s disease
Benztropine (Cogentin)
Anticholinergic adverse effects
ABCDs
Agitation Blurred vision Constipation and confusion Dry mouth Stasis of urine and sweat
Ganglionic blockers
Cholinergic antagonist
Type of cholinergic antagonist.
Nicotine- act on nicotinic receptors of both sympathetic and parasympathetic systems.
Increased GI motility, high BP and HR in low doses.
Neuromuscular blockers
Cholinergic antagonists
Cholinergic antagonist
Block cholinergic transmission between the nerve andinhs and the nicotinic receptors on the skeletal muscle.
Usually, acetylcholine binds to receptors, stimulating Na+ to enter the cell, which in turn causes Ca+ release and muscle contraction.
Depolarizing: (-ium) prevent Na+ from entering the cell. Used for intubation and anesthesia (pancuronium, roc, vec, etc.)
Depolarizing: succinylcholine. Allows Na+ to enter, causing depolarization and vasicilation and then flaccid paralysis. Shorter acting than depolarizing. Can get hyperkalemia, malignant hyperthermia, and prolonged apnea.
Alpha2 agonists
2nd line therapy for HTN.
Activation of central Alpha2 receptors results in a decrease in peripheral outflow of norepinephrine, leading to decreases in peripheral vascular resistance, renal vascular resistance, HR, and BP.
clonidine
Methyldopa: first line therapy in pregnancy.
Most effective when combined with diuretic.
Clorthalidone: clonidine and a thiazides duliuretic
clonidine- decrease in sympathetic tone- decrease in BP. also used for ADHD and withdrawal.
Why is it important to divide the dose of clonidine and methyldopa?
Minimize sedation
Clonidine
Alpha 2 agonist. Best when combined with diuretic.
0.1 mg BID PO. start at lower dose in elderly.
Decreases peripheral resistance
Decreases vascular resistance
Decreases HR and BP
Onset of action: 1/2-1 hr
Duration- 6-10 hrs
Half life: 12-16 hrs
Metabolized by liver, excreted by urine.
ADRs: bradycardia, palpitations, tachycardia, AV block, CP, HF, orthostatic hypotension, EVG changes, syncope, Raynaud’s phenomenon, ER, enuresis, urinary retention.
Do not administer with h/ depression or recent MI.
Prazosin
Alpha 1 antagonist Onset of action as antihypertensive 2 hrs Peak effect 2-4 hrs Half-life- 2-3 hrs Metabolized by liver Excreted in feces. Erastus expensive
Contraindicated in volume depletion and CHF. large deposited in breast milk.
ADRs: orthostatic hypotension, fluid retention, peripheral edema, nasal congestion, blurred vision, dry mouth, constipation, importance, urinalysis frequency. NSAIDs reduce antihypertensive effect.
Alpha1 agonists
Alpha 1 selective: oxymetazoline and phenylephrine. Nasal congestion, acute hypotension.
Atropine
Anticholinergic
Eye- pupillary dilation, decreased ability to focus, and decreases reaction to light(do not give with narrow-angle glaucoma)
GI tract- blocks M2 receptors in GI tract, slowing the system down.
Heart- in higher doses, blocks M2 receptors on SA AV node, which causes tachycardia. Salivary/ sweat/ lacrimary- dries you out.
Drug of choice for bradycardia and heart block.
Contraindications: prostatic hypertrophy, glaucoma, MG, hyperthyroidism, MI, HF unless bradycardia is present
Beta 2 agonist
Beta2- bronchodilators short and long-acting. Albuterol, terbutaline, salmetrol
Epinephrine
Direct acting Alpha agonist. Stimulates alpha and beta receptors.
Directly stimulates cardiac tissues. Increases cardiac contractions, increases HR, vasoconstriction.
Treats anaphylaxis, bradycardia, hypotension, and severe asthma exacerbation.
Onset of action immediate-10 min.
Dobutamine
Adrenergic agonist. Nonselective beta agonist (or Beta 1 agonist?)
Used to improve cardiac output in patients with HF.
onset 1-2 min.
Half-life 2 min
Metabolized in liver
Side effects- HA, HTN, tachycardia
Donezipril (Aricept)
Cholinesterase inhibitor. Presents degradation of acetylcholine. Enhances cholinergic function.
Treat Alzheimer’s. Modest improvement in cognition for 6-9 months.
Effects notes in 6 wks. Can take 18-24 wks for noticeable improvement.
Plasma concentrations 2/3 lower in smokers.
GI side effects common.
Dicyclomine (Bentyl)
Anticholinergics, parasympatholytics.
Adjunct therapy in tx of IBS and PUD
Antispasmodic. Onset 5-10 min, duration 3 hrs
St. John’s wort
Decreases seratonin reptile. Most effective for people with sadness and lesser degrees of depression.
Interacts with MAOIs, TCAs, and SSRIs to cause seratonin syndrome. Decreases digoxin, phenytoin, and cyclosporine levels. May decrease warfarin’ effectiveness. Decreases effectiveness of oral contraceptives.
