CPT1: ANS2 Flashcards
What mechansims of action can parasympathomimetic drugs have?
- direct
- indirect
What general effects do parasympathomimetic drugs have?
- Bradycardia - decreased HR
- hypotension - Low bp
- increased secretions: salivary, bronchial
- smooth muscle contraction
- Bronchoconstriction
- nausea/ vommitting, diaohrea
- increased peristalisis
What do large doses of parasympathomimetic drugs do?
Stimulate then block
Leads to desensitisation of receptors and depolarising block (loss of electrical excitability at the end plate)
What are examples of Muscarinic receptor agonists?
- Pilocarpine
- Bethanechol
What does pilocarpine do?
- Partional agonist selective for MAchR
- Pilocarpine eye drops cross conjuctival membranes (ocular and systemic side effects)
- Causes pupilary ocnstriction and reduction of intraocular pressure
What are side effects of pilocarpine?
Local:
- allergic conjuctivitis
- blurred vision
- cilary spasm
- lid twitching
Systemic
- Nausea,vomitting
- bradycardia (M2)
- Bronchoconstriction (M3)
- Hypotension
What does Bethanechol do?
- Selective MAchR. Doesn’t cross BBB
- Used to alter urinary and GI tract motilty
GI:
- Stimulant laxative (Enhances parasympathetic activity
Bladder:
- Increases tone/ contractility of detrusor muscles and facilitaes voiding (smooth muscle of bladder wall)
What are side effects of bethanechol
- Nausea, Vommitting, bradycardia, hypotension, increased salivation/ secretion/ sweating, bronchoconstriction, increased GI motiltiy
What are general muscularinic agonist side effects?
CVS
- Bradycardia
- Decreased CO
- Decreased force of contraction
- Generalised vasodilation
Smooth Muscle:
- Non-vascular smooth muscle contracts
- GI
- Utrerine
- Detrusor
- Airway
Gland Secretion:
- Salivary
- Sweat glands
- Bronchial
- Pancreatic
- Gastric
What are examples of indirect parasympathomimetic drugs?
Anticholinesterases/ Cholinesterase inhibitors
- Short acting: Edrophonium
- Medium acting: Neostigmine, Donepezil, Rivastigmine
- Long acting:
Galantamine
How do Anticholinesterases work?
Acetylcholinesterases normally break down Acetylcholine. Anticholinesterases inhibit cholinesterases and prevent them form breaking Ach down so it is rounf dor longer to have an effect
Describe the mechanism of action of Edrophonium
- Binds to anionic site of the enzyme
- Readily reversible and short acting
- Administered IV
- used as a diagonstic tool
What is the mechanism of action of Neostigmine, rivastigime and donepezil
- BInds to anionic site of enzyme
- Carbamylates the enzyme which takes minutes to hydrolysis/ reverse
- slow recovery of carbamaylated enzyme means the drug action is prolonged
What drugs are used to treat patients with alzheimers?
How?
RIvastigmine and donepezil
stop Ach being degrades so increase Ach avilability which helps alevate symptoms. Limites use due to adverse effects so these must out weigh benefit.
What are side effects of AchE inhibitors?
What are cautions?
- Nausea, vomitting
- increased GI motility
- Urinary incontinece
- bradycardia
- Asthma
- hepatoxic
- sick sinus syndrome
What are general side effects of Muscularinic antagonists?
inhibition of secretions:
- Salivary and sweat glands
- Gastric secretions- slightly reduced (M1)
- Bronchial glands
Heart Rate:
- Trachycardia (M2)
- Arterial blood pressure unaffected
Smooth Muscle
- Reduced GI motility
- Bronchodilation
- Urinary tract dilation
Examples of muscarinic antagonists
- Atropine and Hyosine: naturally occuring plant compound, readily absorbed in GUT and crosses BBB
- Atropine methonitrate: Atropine derivative, doesnt cross BBB (reduced central side effects)
- Pirenzepine - M1 antagonist. Reduces Gastric acid secretion
- Darifenacin - M3 selective. Reduces bladder contraction
What can muscarinic antagonists be used for?
- Motion sickness - hyosine
- Asthma - short term relief of symptoms (dilation). B2 agonist preferred
- Parkinsons
What is an example of an agonist for both a and b receptors?
What can it be used for?
Adrenaline
- anaphylatic shocks - IM first choice but Iv in emergancy
- decongestant
- cardiac arrest - IV administered
- With local anaesthetics - local anaesthetics cause dilation of blood vessels so adminsistering vasoconstrictor slows rate of absorption and prolongs action
What are systemic effects of a adrenoagonists?
- Vascular smooth muscle contraction (a1)
- skin and splanchnic vacular bed contraction
- large veins, arteries and arterioles vasoconstriction
- Decreased vacular compliance (ability for blood vessels to expand/ relax)
- increased centeral venous pressure
- Increased peripheral resistance
- increased BP intiates bsroreceptor reflex
- cerebral/ conary/ pulmonsry beds unaffected
- increased cardiac work
What are examples of a agonists?
- Phenylephrine - a1 (decongestant)
- clonidine - a2 (acts centerally)
What effects do phenylephrine have?
Side effects?
- constriction of blood vessels
- constriction of nasal passage ways
- reduction in swelling
What effects does clonidine have?
side effects?
- Hypertension and migrane
- centerally acting hypertensive
- decreases CO and peripheral resistance
- cant withdrawl suddenly
Causes blood vessels to relax and treats hypertension
- Sedatative
- depression
- fluid retention
- constipation
What are general actions of B adrenoagonists?
Smooth muscle:
- Relaxation of smooth muscle B2
- Vaso dilation B2 (mainly endothelium dependent). Relaxation not just mediated by cAMP but also BKCa channels
- B3 mediated signalling not just by cAMP but also by delayed rectifier K+ channels
Nerve terminals:
- a2 - inhibitory (inhibits NT release)
- B2 - facilitates NT release
Heart:
- B1 - increase force and rate
- increased CO and O2 consumption
Metabolism
- Encourages conversion of energy stores to fuels. B1/2 - liver and muscle carbohydrate metabolism. B3 - lipolysis. a2 - insulin secretion decreased
SKeletal
- Tremor or shaking
What are examples of B agonists?
- b1 - dobutamine - septic shock. Increased contractility. Iv administration
- B2 - salbutamol - bronchodilation. Uterine smooth muscle dilation
Clinical effects of adrenoreceptor antagonists
- MI
- Angina
- heart failure
- hypertension
- dysrhymias
Anxiety
migranes
Examples of a antagonists
effects?
- a1 - prazosine, doxazosine
- vasodilation and fall in arterial pressure
- blockage of a1 mediated vasoconstriction
- increased CO as drop in BP detected by baroreceptors which increase sympatheitc response
- Smooth muscle relaxation
- additional blockage of a2 - increases #NT release
b antagonist examples
- Propranolol: B1/2
- Oxprenolol: non selective
- Nebivilol: B1/ NO
- Atenalol: B1
*
What are the exceptions to effects of propanolol?
- at rest propranol doesnt effect HR, CO, atria pressure
- depends on degree of sympathetic activity
Effects of B antagonists
- Bronchoconstriction
- cardiac depression
- bradycardia
- hypoglycemia
- fatigue - reduced CO/ muscle perfusion
- cold extremitoes - reduced B vasodilation
